MEF2A_HUMAN
ID MEF2A_HUMAN Reviewed; 507 AA.
AC Q02078; B4DFQ7; F6XG23; O43814; Q14223; Q14224; Q59GX4; Q7Z6C9; Q96D14;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Myocyte-specific enhancer factor 2A;
DE AltName: Full=Serum response factor-like protein 1;
GN Name=MEF2A; Synonyms=MEF2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS MEF2; RSRFC4 AND RSRFC9), DNA-BINDING,
RP TISSUE SPECIFICITY, AND DIMERIZATION.
RC TISSUE=Placenta;
RX PubMed=1748287; DOI=10.1101/gad.5.12a.2327;
RA Pollock R., Treisman R.;
RT "Human SRF-related proteins: DNA-binding properties and potential
RT regulatory targets.";
RL Genes Dev. 5:2327-2341(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM RSRFC9), AND SEQUENCE REVISION.
RA Treisman R.;
RL Submitted (NOV-1993) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS MEF2 AND RSRFC9), AND TISSUE
RP SPECIFICITY.
RC TISSUE=Heart, and Skeletal muscle;
RX PubMed=1516833; DOI=10.1101/gad.6.9.1783;
RA Yu Y.-T., Breitbart R.E., Smoot L.B., Lee Y., Mahdavi V., Nadal-Ginard B.;
RT "Human myocyte-specific enhancer factor 2 comprises a group of tissue-
RT restricted MADS box transcription factors.";
RL Genes Dev. 6:1783-1798(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS RSRFC4 AND RSRFC9).
RA Suzuki E., Lowry J., Sonoda G., Testa J.R., Walsh K.;
RL Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7).
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno F.R.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 5 AND 8).
RC TISSUE=Pancreas, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP INTERACTION WITH MAPK7, AND PHOSPHORYLATION.
RX PubMed=9753748; DOI=10.1093/nar/26.20.4771;
RA Yang C.-C., Ornatsky O.I., McDermott J.C., Cruz T.F., Prody C.A.;
RT "Interaction of myocyte enhancer factor 2 (MEF2) with a mitogen-activated
RT protein kinase, ERK5/BMK1.";
RL Nucleic Acids Res. 26:4771-4777(1998).
RN [10]
RP INTERACTION WITH HDAC4 AND HDAC9.
RX PubMed=10487761; DOI=10.1093/emboj/18.18.5099;
RA Miska E.A., Karlsson C., Langley E., Nielsen S.J., Pines J., Kouzarides T.;
RT "HDAC4 deacetylase associates with and represses the MEF2 transcription
RT factor.";
RL EMBO J. 18:5099-5107(1999).
RN [11]
RP PHOSPHORYLATION AT THR-312; THR-319 AND SER-453, FUNCTION,
RP HETERODIMERIZATION, AND MUTAGENESIS OF THR-312; THR-319; SER-355; SER-453
RP AND SER-479.
RX PubMed=9858528; DOI=10.1128/mcb.19.1.21;
RA Zhao M., New L., Kravchenko V.V., Kato Y., Gram H., di Padova F.,
RA Olson E.N., Ulevitch R.J., Han J.-D.;
RT "Regulation of the MEF2 family of transcription factors by p38.";
RL Mol. Cell. Biol. 19:21-30(1999).
RN [12]
RP INTERACTION WITH MAPK14, PHOSPHORYLATION AT THR-312 AND THR-319, AND
RP MUTAGENESIS OF ARG-269; LYS-270; LEU-273; VAL-275; ILE-277 AND PRO-278.
RX PubMed=10330143; DOI=10.1128/mcb.19.6.4028;
RA Yang S.-H., Galanis A., Sharrocks A.D.;
RT "Targeting of p38 mitogen-activated protein kinases to MEF2 transcription
RT factors.";
RL Mol. Cell. Biol. 19:4028-4038(1999).
RN [13]
RP PHOSPHORYLATION AT THR-312; THR-319 AND SER-355, AND MUTAGENESIS OF
RP THR-312; THR-319 AND SER-355.
RX PubMed=10849446; DOI=10.1074/jbc.m001573200;
RA Kato Y., Zhao M., Morikawa A., Sugiyama T., Chakravortty D., Koide N.,
RA Yoshida T., Tapping R.I., Yang Y., Yokochi T., Lee J.D.;
RT "Big mitogen-activated kinase regulates multiple members of the MEF2
RT protein family.";
RL J. Biol. Chem. 275:18534-18540(2000).
RN [14]
RP PROTEOLYTIC PROCESSING AT ASP-176; ASP-213 AND ASP-466, FUNCTION, AND
RP MUTAGENESIS OF ASP-176 AND ASP-213.
RX PubMed=11904443; DOI=10.1073/pnas.022036399;
RA Okamoto S., Li Z., Ju C., Scholzke M.N., Mathews E., Cui J., Salvesen G.S.,
RA Bossy-Wetzel E., Lipton S.A.;
RT "Dominant-interfering forms of MEF2 generated by caspase cleavage
RT contribute to NMDA-induced neuronal apoptosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:3974-3979(2002).
RN [15]
RP PHOSPHORYLATION AT SER-255; THR-312; THR-319 AND SER-408, IDENTIFICATION BY
RP MASS SPECTROMETRY, AND MUTAGENESIS OF SER-255.
RX PubMed=12586839; DOI=10.1074/jbc.m211312200;
RA Cox D.M., Du M., Marback M., Yang E.C.C., Chan J., Siu K.W.M.,
RA McDermott J.C.;
RT "Phosphorylation motifs regulating the stability and function of myocyte
RT enhancer factor 2A.";
RL J. Biol. Chem. 278:15297-15303(2003).
RN [16]
RP PHOSPHORYLATION AT SER-408, FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS
RP OF SER-408.
RX PubMed=12691662; DOI=10.1016/s0896-6273(03)00191-0;
RA Gong X., Tang X., Wiedmann M., Wang X., Peng J., Zheng D., Blair L.A.C.,
RA Marshall J., Mao Z.;
RT "Cdk5-mediated inhibition of the protective effects of transcription factor
RT MEF2 in neurotoxicity-induced apoptosis.";
RL Neuron 38:33-46(2003).
RN [17]
RP INTERACTION WITH SLC2A4RG.
RX PubMed=14630949; DOI=10.1073/pnas.2432756100;
RA Knight J.B., Eyster C.A., Griesel B.A., Olson A.L.;
RT "Regulation of the human GLUT4 gene promoter: interaction between a
RT transcriptional activator and myocyte enhancer factor 2A.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:14725-14730(2003).
RN [18]
RP FUNCTION OF BETA DOMAIN.
RX PubMed=15834131; DOI=10.1074/jbc.m502491200;
RA Zhu B., Ramachandran B., Gulick T.;
RT "Alternative pre-mRNA splicing governs expression of a conserved acidic
RT transactivation domain in myocyte enhancer factor 2 factors of striated
RT muscle and brain.";
RL J. Biol. Chem. 280:28749-28760(2005).
RN [19]
RP PROTEOLYTIC PROCESSING, AND PHOSPHORYLATION.
RX PubMed=15888658; DOI=10.1523/jneurosci.1331-05.2005;
RA Tang X., Wang X., Gong X., Tong M., Park D., Xia Z., Mao Z.;
RT "Cyclin-dependent kinase 5 mediates neurotoxin-induced degradation of the
RT transcription factor myocyte enhancer factor 2.";
RL J. Neurosci. 25:4823-4834(2005).
RN [20]
RP SUMOYLATION AT LYS-403, INTERACTION WITH PIAS1, FUNCTION, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF LYS-403.
RX PubMed=16563226; DOI=10.1111/j.1582-4934.2006.tb00295.x;
RA Riquelme C., Barthel K.K., Liu X.;
RT "SUMO-1 modification of MEF2A regulates its transcriptional activity.";
RL J. Cell. Mol. Med. 10:132-144(2006).
RN [21]
RP SUMOYLATION AT LYS-403, PHOSPHORYLATION AT SER-408, FUNCTION, AND
RP MUTAGENESIS OF LYS-403 AND SER-408.
RX PubMed=16371476; DOI=10.1073/pnas.0503698102;
RA Hietakangas V., Anckar J., Blomster H.A., Fujimoto M., Palvimo J.J.,
RA Nakai A., Sistonen L.;
RT "PDSM, a motif for phosphorylation-dependent SUMO modification.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:45-50(2006).
RN [22]
RP PHOSPHORYLATION AT SER-408, AND FUNCTION.
RX PubMed=16484498; DOI=10.1126/science.1122513;
RA Shalizi A., Gaudilliere B., Yuan Z., Stegmueller J., Shirogane T., Ge Q.,
RA Tan Y., Schulman B., Harper J.W., Bonni A.;
RT "A calcium-regulated MEF2 sumoylation switch controls postsynaptic
RT differentiation.";
RL Science 311:1012-1017(2006).
RN [23]
RP PHOSPHORYLATION AT THR-312 BY NLK.
RX PubMed=17785444; DOI=10.1128/mcb.01481-07;
RA Satoh K., Ohnishi J., Sato A., Takeyama M., Iemura S., Natsume T.,
RA Shibuya H.;
RT "Nemo-like kinase-myocyte enhancer factor 2A signaling regulates anterior
RT formation in Xenopus development.";
RL Mol. Cell. Biol. 27:7623-7630(2007).
RN [24]
RP ACETYLATION, AND INVOLVEMENT IN CARDIAC HYPERTROPHY.
RX PubMed=18697823; DOI=10.1161/circulationaha.107.760488;
RA Wei J.Q., Shehadeh L.A., Mitrani J.M., Pessanha M., Slepak T.I.,
RA Webster K.A., Bishopric N.H.;
RT "Quantitative control of adaptive cardiac hypertrophy by acetyltransferase
RT p300.";
RL Circulation 118:934-946(2008).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98; SER-235 AND SER-255,
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98 (ISOFORMS 6; MEFA AND
RP RSRFC9), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-30 (ISOFORMS 7 AND
RP 8), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-249, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [28]
RP FUNCTION, AND CHROMATIN BINDING.
RX PubMed=21468593; DOI=10.3892/mmr.2011.465;
RA Liu X., Jin E.Z., Zhi J.X., Li X.Q.;
RT "Identification of HZF1 as a novel target gene of the MEF2 transcription
RT factor.";
RL Mol. Med. Report. 4:465-469(2011).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98 AND SER-255, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [30]
RP VARIANTS SER-263; LEU-279 AND ASP-283, AND CHARACTERIZATION OF VARIANTS
RP SER-263; LEU-279 AND ASP-283.
RX PubMed=15496429; DOI=10.1093/hmg/ddh329;
RA Bhagavatula M.R.K., Fan C., Shen G.-Q., Cassano J., Plow E.F., Topol E.J.,
RA Wang Q.;
RT "Transcription factor MEF2A mutations in patients with coronary artery
RT disease.";
RL Hum. Mol. Genet. 13:3181-3188(2004).
RN [31]
RP VARIANT LEU-279, AND ASSOCIATION WITH SUSCEPTIBILITY TO MYOCARDIAL
RP INFARCTION.
RX PubMed=15958500; DOI=10.1136/jmg.2005.035071;
RA Gonzalez P., Garcia-Castro M., Reguero J.R., Batalla A., Ordonez A.G.,
RA Palop R.L., Lozano I., Montes M., Alvarez V., Coto E.;
RT "The Pro279Leu variant in the transcription factor MEF2A is associated with
RT myocardial infarction.";
RL J. Med. Genet. 43:167-169(2006).
RN [32]
RP VARIANT LEU-279, AND LACK OF ASSOCIATION WITH MYOCARDIAL INFARCTION.
RX PubMed=18086930; DOI=10.1161/circulationaha.107.728485;
RA Lieb W., Mayer B., Koenig I.R., Borwitzky I., Goetz A., Kain S.,
RA Hengstenberg C., Linsel-Nitschke P., Fischer M., Doering A., Wichmann H.E.,
RA Meitinger T., Kreutz R., Ziegler A., Schunkert H., Erdmann J.;
RT "Lack of association between the MEF2A gene and myocardial infarction.";
RL Circulation 117:185-191(2008).
RN [33]
RP STRUCTURE BY NMR OF 2-86 IN COMPLEX WITH DNA.
RX PubMed=10835359; DOI=10.1093/emboj/19.11.2615;
RA Huang K., Louis J.M., Donaldson L., Lim F.L., Sharrocks A.D., Clore G.M.;
RT "Solution structure of the MEF2A-DNA complex: structural basis for the
RT modulation of DNA bending and specificity by MADS-box transcription
RT factors.";
RL EMBO J. 19:2615-2628(2000).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 2-78 IN COMPLEX WITH DNA, AND
RP DIMERIZATION.
RX PubMed=10715212; DOI=10.1006/jmbi.2000.3568;
RA Santelli E., Richmond T.J.;
RT "Crystal structure of MEF2A core bound to DNA at 1.5 A resolution.";
RL J. Mol. Biol. 297:437-449(2000).
CC -!- FUNCTION: Transcriptional activator which binds specifically to the
CC MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific
CC genes. Also involved in the activation of numerous growth factor- and
CC stress-induced genes. Mediates cellular functions not only in skeletal
CC and cardiac muscle development, but also in neuronal differentiation
CC and survival. Plays diverse roles in the control of cell growth,
CC survival and apoptosis via p38 MAPK signaling in muscle-specific and/or
CC growth factor-related transcription. In cerebellar granule neurons,
CC phosphorylated and sumoylated MEF2A represses transcription of NUR77
CC promoting synaptic differentiation. Associates with chromatin to the
CC ZNF16 promoter. {ECO:0000269|PubMed:11904443,
CC ECO:0000269|PubMed:12691662, ECO:0000269|PubMed:15834131,
CC ECO:0000269|PubMed:16371476, ECO:0000269|PubMed:16484498,
CC ECO:0000269|PubMed:16563226, ECO:0000269|PubMed:21468593,
CC ECO:0000269|PubMed:9858528}.
CC -!- SUBUNIT: Binds DNA as a homo- or heterodimer. Dimerizes with MEF2D.
CC Interacts with HDAC7 (By similarity). Interacts with PIAS1; the
CC interaction enhances sumoylation. Interacts with HDAC4, HDAC9 and
CC SLC2A4RG. Interacts (via the N-terminal) with MAPK7; the interaction
CC results in the phosphorylation and transcriptional activity of MEF2A.
CC {ECO:0000250, ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:10487761,
CC ECO:0000269|PubMed:10715212, ECO:0000269|PubMed:10835359,
CC ECO:0000269|PubMed:14630949, ECO:0000269|PubMed:16563226,
CC ECO:0000269|PubMed:9753748}.
CC -!- INTERACTION:
CC Q02078; Q99697-3: PITX2; NbExp=2; IntAct=EBI-2656305, EBI-1175243;
CC Q02078; P10085: Myod1; Xeno; NbExp=2; IntAct=EBI-2656305, EBI-4405734;
CC Q02078; P70257-2: Nfix; Xeno; NbExp=2; IntAct=EBI-2656305, EBI-2639084;
CC Q02078-1; P63165: SUMO1; NbExp=3; IntAct=EBI-15799584, EBI-80140;
CC Q02078-2; P50221: MEOX1; NbExp=3; IntAct=EBI-16431401, EBI-2864512;
CC Q02078-5; P56524-2: HDAC4; NbExp=3; IntAct=EBI-12232917, EBI-11953488;
CC Q02078-5; O75031: HSF2BP; NbExp=3; IntAct=EBI-12232917, EBI-7116203;
CC Q02078-6; Q13164: MAPK7; NbExp=3; IntAct=EBI-16437973, EBI-1213983;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00251,
CC ECO:0000269|PubMed:12691662, ECO:0000269|PubMed:16563226}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=MEF2;
CC IsoId=Q02078-1; Sequence=Displayed;
CC Name=MEFA;
CC IsoId=Q02078-2; Sequence=VSP_006240;
CC Name=RSRFC4;
CC IsoId=Q02078-3; Sequence=VSP_006241, VSP_006242;
CC Name=RSRFC9;
CC IsoId=Q02078-4; Sequence=VSP_006240, VSP_006241, VSP_006242;
CC Name=5;
CC IsoId=Q02078-5; Sequence=VSP_006241;
CC Name=6;
CC IsoId=Q02078-6; Sequence=VSP_006240, VSP_006241;
CC Name=7;
CC IsoId=Q02078-7; Sequence=VSP_043338, VSP_006240;
CC Name=8;
CC IsoId=Q02078-8; Sequence=VSP_046018, VSP_046019, VSP_006241;
CC -!- TISSUE SPECIFICITY: Isoform MEF2 and isoform MEFA are expressed only in
CC skeletal and cardiac muscle and in the brain. Isoform RSRFC4 and
CC isoform RSRFC9 are expressed in all tissues examined.
CC {ECO:0000269|PubMed:1516833, ECO:0000269|PubMed:1748287}.
CC -!- PTM: Constitutive phosphorylation on Ser-408 promotes Lys-403
CC sumoylation thus preventing acetylation at this site. Dephosphorylation
CC on Ser-408 by PPP3CA upon neuron depolarization promotes a switch from
CC sumoylation to acetylation on residue Lys-403 leading to inhibition of
CC dendrite claw differentiation. Phosphorylation on Thr-312 and Thr-319
CC are the main sites involved in p38 MAPK signaling and activate
CC transcription. Phosphorylated on these sites by MAPK14/p38alpha and
CC MAPK11/p38beta, but not by MAPK13/p38delta nor by MAPK12/p38gamma.
CC Phosphorylation on Ser-408 by CDK5 induced by neurotoxicity inhibits
CC MEF2A transcriptional activation leading to apoptosis of cortical
CC neurons. Phosphorylation on Thr-312, Thr-319 and Ser-355 can be induced
CC by EGF. {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:10849446,
CC ECO:0000269|PubMed:12586839, ECO:0000269|PubMed:12691662,
CC ECO:0000269|PubMed:15888658, ECO:0000269|PubMed:16371476,
CC ECO:0000269|PubMed:16484498, ECO:0000269|PubMed:16563226,
CC ECO:0000269|PubMed:17785444, ECO:0000269|PubMed:9753748,
CC ECO:0000269|PubMed:9858528}.
CC -!- PTM: Sumoylation on Lys-403 is enhanced by PIAS1 and represses
CC transcriptional activity. Phosphorylation on Ser-408 is required for
CC sumoylation. Has no effect on nuclear location nor on DNA binding.
CC Sumoylated with SUMO1 and, to a lesser extent with SUMO2 and SUMO3.
CC PIASx facilitates sumoylation in postsynaptic dendrites in the
CC cerebellar cortex and promotes their morphogenesis (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Acetylation on Lys-403 activates transcriptional activity.
CC Acetylated by p300 on several sites in diffentiating myocytes.
CC Acetylation on Lys-4 increases DNA binding and transactivation (By
CC similarity). Hyperacetylation by p300 leads to enhanced cardiac myocyte
CC growth and heart failure. {ECO:0000250}.
CC -!- PTM: Proteolytically cleaved in cerebellar granule neurons on several
CC sites by caspase 3 and caspase 7 following neurotoxicity.
CC Preferentially cleaves the CDK5-mediated hyperphosphorylated form which
CC leads to neuron apoptosis and transcriptional inactivation.
CC {ECO:0000269|PubMed:11904443, ECO:0000269|PubMed:15888658}.
CC -!- DISEASE: Coronary artery disease, autosomal dominant, 1 (ADCAD1)
CC [MIM:608320]: A common heart disease characterized by reduced or absent
CC blood flow in one or more of the arteries that encircle and supply the
CC heart. Its most important complication is acute myocardial infarction.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the MEF2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH53871.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD92222.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; Y16312; CAA76175.1; -; mRNA.
DR EMBL; X63381; CAA44979.1; -; mRNA.
DR EMBL; X68503; CAA48516.1; -; mRNA.
DR EMBL; X68505; CAA48517.1; -; mRNA.
DR EMBL; U49020; AAB17195.1; -; Genomic_DNA.
DR EMBL; U44889; AAB17195.1; JOINED; Genomic_DNA.
DR EMBL; U49012; AAB17195.1; JOINED; Genomic_DNA.
DR EMBL; U49013; AAB17195.1; JOINED; Genomic_DNA.
DR EMBL; U49015; AAB17195.1; JOINED; Genomic_DNA.
DR EMBL; U49016; AAB17195.1; JOINED; Genomic_DNA.
DR EMBL; U49017; AAB17195.1; JOINED; Genomic_DNA.
DR EMBL; U49018; AAB17195.1; JOINED; Genomic_DNA.
DR EMBL; U49019; AAB17195.1; JOINED; Genomic_DNA.
DR EMBL; U49020; AAB17196.1; -; Genomic_DNA.
DR EMBL; U44889; AAB17196.1; JOINED; Genomic_DNA.
DR EMBL; U49012; AAB17196.1; JOINED; Genomic_DNA.
DR EMBL; U49013; AAB17196.1; JOINED; Genomic_DNA.
DR EMBL; U49015; AAB17196.1; JOINED; Genomic_DNA.
DR EMBL; U49016; AAB17196.1; JOINED; Genomic_DNA.
DR EMBL; U49017; AAB17196.1; JOINED; Genomic_DNA.
DR EMBL; U49018; AAB17196.1; JOINED; Genomic_DNA.
DR EMBL; U49019; AAB17196.1; JOINED; Genomic_DNA.
DR EMBL; AK294207; BAG57518.1; -; mRNA.
DR EMBL; AB208985; BAD92222.1; ALT_INIT; mRNA.
DR EMBL; AC015660; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC022692; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC103967; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC013437; AAH13437.1; -; mRNA.
DR EMBL; BC053871; AAH53871.1; ALT_INIT; mRNA.
DR CCDS; CCDS45362.1; -. [Q02078-5]
DR CCDS; CCDS45363.1; -. [Q02078-7]
DR CCDS; CCDS53978.1; -. [Q02078-6]
DR CCDS; CCDS58401.1; -. [Q02078-8]
DR CCDS; CCDS81920.1; -. [Q02078-2]
DR PIR; C39481; C39481.
DR PIR; S25831; S25831.
DR RefSeq; NP_001124399.1; NM_001130927.2. [Q02078-7]
DR RefSeq; NP_001124400.1; NM_001130928.2. [Q02078-8]
DR RefSeq; NP_001165365.1; NM_001171894.2. [Q02078-6]
DR RefSeq; NP_001306135.1; NM_001319206.1. [Q02078-2]
DR RefSeq; NP_005578.2; NM_005587.3. [Q02078-5]
DR RefSeq; XP_011519883.1; XM_011521581.2.
DR RefSeq; XP_011519884.1; XM_011521582.2. [Q02078-1]
DR RefSeq; XP_011519888.1; XM_011521586.2.
DR RefSeq; XP_016877679.1; XM_017022190.1.
DR RefSeq; XP_016877680.1; XM_017022191.1. [Q02078-1]
DR RefSeq; XP_016877682.1; XM_017022193.1.
DR RefSeq; XP_016877683.1; XM_017022194.1.
DR PDB; 1C7U; NMR; -; A/B=2-86.
DR PDB; 1EGW; X-ray; 1.50 A; A/B/C/D=2-78.
DR PDB; 1LEW; X-ray; 2.30 A; B=269-280.
DR PDB; 3KOV; X-ray; 2.90 A; A/B/I/J=2-91.
DR PDB; 3MU6; X-ray; 2.43 A; A/B/C/D=2-70.
DR PDB; 3P57; X-ray; 2.19 A; A/B/C/D/I/J=2-91.
DR PDB; 6BYY; X-ray; 2.30 A; A/B/C/D=1-64, A/B/C/D=92-95.
DR PDB; 6BZ1; X-ray; 2.97 A; A/B/C/D=1-64, A/B/C/D=92-95.
DR PDBsum; 1C7U; -.
DR PDBsum; 1EGW; -.
DR PDBsum; 1LEW; -.
DR PDBsum; 3KOV; -.
DR PDBsum; 3MU6; -.
DR PDBsum; 3P57; -.
DR PDBsum; 6BYY; -.
DR PDBsum; 6BZ1; -.
DR AlphaFoldDB; Q02078; -.
DR SMR; Q02078; -.
DR BioGRID; 110369; 68.
DR CORUM; Q02078; -.
DR DIP; DIP-40711N; -.
DR IntAct; Q02078; 49.
DR MINT; Q02078; -.
DR STRING; 9606.ENSP00000346389; -.
DR GlyGen; Q02078; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q02078; -.
DR PhosphoSitePlus; Q02078; -.
DR BioMuta; MEF2A; -.
DR EPD; Q02078; -.
DR jPOST; Q02078; -.
DR MassIVE; Q02078; -.
DR MaxQB; Q02078; -.
DR PaxDb; Q02078; -.
DR PeptideAtlas; Q02078; -.
DR PRIDE; Q02078; -.
DR ProteomicsDB; 28155; -.
DR ProteomicsDB; 58035; -. [Q02078-1]
DR ProteomicsDB; 58036; -. [Q02078-2]
DR ProteomicsDB; 58037; -. [Q02078-3]
DR ProteomicsDB; 58038; -. [Q02078-4]
DR ProteomicsDB; 58039; -. [Q02078-5]
DR ProteomicsDB; 58040; -. [Q02078-6]
DR ProteomicsDB; 58041; -. [Q02078-7]
DR Antibodypedia; 3854; 1075 antibodies from 44 providers.
DR DNASU; 4205; -.
DR Ensembl; ENST00000354410.9; ENSP00000346389.5; ENSG00000068305.18. [Q02078-5]
DR Ensembl; ENST00000449277.6; ENSP00000399460.2; ENSG00000068305.18. [Q02078-8]
DR Ensembl; ENST00000557785.5; ENSP00000453441.1; ENSG00000068305.18. [Q02078-6]
DR Ensembl; ENST00000557942.6; ENSP00000453095.1; ENSG00000068305.18. [Q02078-2]
DR Ensembl; ENST00000558812.5; ENSP00000454120.1; ENSG00000068305.18. [Q02078-7]
DR Ensembl; ENST00000686611.1; ENSP00000509137.1; ENSG00000068305.18. [Q02078-1]
DR Ensembl; ENST00000691492.1; ENSP00000509537.1; ENSG00000068305.18. [Q02078-6]
DR GeneID; 4205; -.
DR KEGG; hsa:4205; -.
DR MANE-Select; ENST00000557942.6; ENSP00000453095.1; NM_001319206.4; NP_001306135.1. [Q02078-2]
DR UCSC; uc002bve.4; human. [Q02078-1]
DR CTD; 4205; -.
DR DisGeNET; 4205; -.
DR GeneCards; MEF2A; -.
DR HGNC; HGNC:6993; MEF2A.
DR HPA; ENSG00000068305; Low tissue specificity.
DR MalaCards; MEF2A; -.
DR MIM; 600660; gene.
DR MIM; 608320; phenotype.
DR neXtProt; NX_Q02078; -.
DR OpenTargets; ENSG00000068305; -.
DR Orphanet; 411969; NON RARE IN EUROPE: Metabolic syndrome.
DR PharmGKB; PA30731; -.
DR VEuPathDB; HostDB:ENSG00000068305; -.
DR eggNOG; KOG0014; Eukaryota.
DR GeneTree; ENSGT00940000156205; -.
DR HOGENOM; CLU_022902_4_0_1; -.
DR InParanoid; Q02078; -.
DR OMA; MNTQRIS; -.
DR OrthoDB; 729387at2759; -.
DR PhylomeDB; Q02078; -.
DR TreeFam; TF314067; -.
DR PathwayCommons; Q02078; -.
DR Reactome; R-HSA-198753; ERK/MAPK targets.
DR Reactome; R-HSA-525793; Myogenesis.
DR SignaLink; Q02078; -.
DR SIGNOR; Q02078; -.
DR BioGRID-ORCS; 4205; 10 hits in 1104 CRISPR screens.
DR ChiTaRS; MEF2A; human.
DR EvolutionaryTrace; Q02078; -.
DR GeneWiki; Myocyte-specific_enhancer_factor_2A; -.
DR GenomeRNAi; 4205; -.
DR Pharos; Q02078; Tbio.
DR PRO; PR:Q02078; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q02078; protein.
DR Bgee; ENSG00000068305; Expressed in calcaneal tendon and 203 other tissues.
DR ExpressionAtlas; Q02078; baseline and differential.
DR Genevisible; Q02078; HS.
DR GO; GO:0000785; C:chromatin; ISS:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IDA:BHF-UCL.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0035035; F:histone acetyltransferase binding; IPI:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0046332; F:SMAD binding; IPI:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0061337; P:cardiac conduction; ISS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0071277; P:cellular response to calcium ion; IDA:UniProtKB.
DR GO; GO:0048813; P:dendrite morphogenesis; ISS:UniProtKB.
DR GO; GO:0070375; P:ERK5 cascade; IMP:UniProtKB.
DR GO; GO:0007507; P:heart development; IEP:UniProtKB.
DR GO; GO:0000165; P:MAPK cascade; IDA:UniProtKB.
DR GO; GO:0000002; P:mitochondrial genome maintenance; ISS:UniProtKB.
DR GO; GO:0048311; P:mitochondrion distribution; ISS:UniProtKB.
DR GO; GO:0007517; P:muscle organ development; NAS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IDA:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0046326; P:positive regulation of glucose import; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006351; P:transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0055005; P:ventricular cardiac myofibril assembly; ISS:UniProtKB.
DR CDD; cd00265; MADS_MEF2_like; 1.
DR DisProt; DP01925; -.
DR Gene3D; 3.40.1810.10; -; 1.
DR IDEAL; IID00240; -.
DR InterPro; IPR022102; HJURP_C.
DR InterPro; IPR033896; MADS_MEF2-like.
DR InterPro; IPR002100; TF_MADSbox.
DR InterPro; IPR036879; TF_MADSbox_sf.
DR Pfam; PF12347; HJURP_C; 1.
DR Pfam; PF00319; SRF-TF; 1.
DR PRINTS; PR00404; MADSDOMAIN.
DR SMART; SM00432; MADS; 1.
DR SUPFAM; SSF55455; SSF55455; 1.
DR PROSITE; PS00350; MADS_BOX_1; 1.
DR PROSITE; PS50066; MADS_BOX_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative splicing; Apoptosis;
KW Developmental protein; Differentiation; Disease variant; DNA-binding;
KW Isopeptide bond; Neurogenesis; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..507
FT /note="Myocyte-specific enhancer factor 2A"
FT /id="PRO_0000199428"
FT DOMAIN 3..57
FT /note="MADS-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00251"
FT DNA_BIND 58..86
FT /note="Mef2-type"
FT /evidence="ECO:0000255"
FT REGION 173..229
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 243..270
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 266..283
FT /note="Required for interaction with MAPKs"
FT REGION 289..296
FT /note="Beta domain"
FT REGION 397..507
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 428..448
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 450..466
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 176..177
FT /note="Cleavage"
FT /evidence="ECO:0000305"
FT SITE 213..214
FT /note="Cleavage"
FT /evidence="ECO:0000305"
FT SITE 466..467
FT /note="Cleavage"
FT /evidence="ECO:0000305"
FT MOD_RES 59
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 235
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 249
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 255
FT /note="Phosphoserine; by MAPK14"
FT /evidence="ECO:0000269|PubMed:12586839,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT MOD_RES 312
FT /note="Phosphothreonine; by MAPK7 and MAPK14"
FT /evidence="ECO:0000269|PubMed:10330143,
FT ECO:0000269|PubMed:10849446, ECO:0000269|PubMed:12586839,
FT ECO:0000269|PubMed:17785444, ECO:0000269|PubMed:9858528"
FT MOD_RES 312
FT /note="Phosphothreonine; by NLK"
FT /evidence="ECO:0000269|PubMed:10330143,
FT ECO:0000269|PubMed:10849446, ECO:0000269|PubMed:12586839,
FT ECO:0000269|PubMed:17785444, ECO:0000269|PubMed:9858528"
FT MOD_RES 319
FT /note="Phosphothreonine; by MAPK7 and MAPK14"
FT /evidence="ECO:0000269|PubMed:10330143,
FT ECO:0000269|PubMed:10849446, ECO:0000269|PubMed:12586839,
FT ECO:0000269|PubMed:9858528"
FT MOD_RES 355
FT /note="Phosphoserine; by MAPK7"
FT /evidence="ECO:0000269|PubMed:10849446"
FT MOD_RES 403
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q2MJT0"
FT MOD_RES 408
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000269|PubMed:12586839,
FT ECO:0000269|PubMed:12691662, ECO:0000269|PubMed:16371476,
FT ECO:0000269|PubMed:16484498"
FT MOD_RES 415
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q60929"
FT MOD_RES 453
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000269|PubMed:9858528"
FT CROSSLNK 403
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT VAR_SEQ 19..86
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043338"
FT VAR_SEQ 19..62
FT /note="VTFTKRKFGLMKKAYELSVLCDCEIALIIFNSSNKLFQYASTDM -> TLRK
FT KGLNGCESPDADDYFEHSPLSEDRFSKLNEDSDFIFKRGP (in isoform 8)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_046018"
FT VAR_SEQ 63..132
FT /note="Missing (in isoform 8)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_046019"
FT VAR_SEQ 87..132
FT /note="ALNKKEHRGCDSPDPDTSYVLTPHTEEKYKKINEEFDNMMRNHKIA -> TL
FT RKKGLNGCESPDADDYFEHSPLSEDRFSKLNEDSDFIFKRGP (in isoform
FT MEFA, isoform RSRFC9, isoform 6 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:1516833, ECO:0000303|PubMed:1748287,
FT ECO:0000303|Ref.2, ECO:0000303|Ref.6"
FT /id="VSP_006240"
FT VAR_SEQ 289..296
FT /note="Missing (in isoform RSRFC4, isoform RSRFC9, isoform
FT 5, isoform 6 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:1516833,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:1748287,
FT ECO:0000303|Ref.2, ECO:0000303|Ref.6"
FT /id="VSP_006241"
FT VAR_SEQ 420..421
FT /note="Missing (in isoform RSRFC4 and isoform RSRFC9)"
FT /evidence="ECO:0000303|PubMed:1516833,
FT ECO:0000303|PubMed:1748287, ECO:0000303|Ref.2"
FT /id="VSP_006242"
FT VARIANT 263
FT /note="N -> S (in dbSNP:rs121918530)"
FT /evidence="ECO:0000269|PubMed:15496429"
FT /id="VAR_038407"
FT VARIANT 279
FT /note="P -> L (in dbSNP:rs121918529)"
FT /evidence="ECO:0000269|PubMed:15496429,
FT ECO:0000269|PubMed:15958500, ECO:0000269|PubMed:18086930"
FT /id="VAR_038408"
FT VARIANT 283
FT /note="G -> D"
FT /evidence="ECO:0000269|PubMed:15496429"
FT /id="VAR_038409"
FT VARIANT 440..446
FT /note="Missing (loss of nuclear localization; 66% decrease
FT in transcription activation; loss of synergistic activation
FT by MEF2A and GATA1 through a dominant-negative mechanism)"
FT /id="VAR_017743"
FT MUTAGEN 176
FT /note="D->A: Abolishes cleavage at sites 1 and 2 by caspase
FT 3. Increased cleavage at site 3 by caspase 3."
FT /evidence="ECO:0000269|PubMed:11904443"
FT MUTAGEN 213
FT /note="D->A: Abolishes cleavage at sites 2 and 3 by caspase
FT 7."
FT /evidence="ECO:0000269|PubMed:11904443"
FT MUTAGEN 255
FT /note="S->A: Slightly increased MEF2A protein level."
FT /evidence="ECO:0000269|PubMed:12586839"
FT MUTAGEN 255
FT /note="S->D: Decreased MEF2A protein level."
FT /evidence="ECO:0000269|PubMed:12586839"
FT MUTAGEN 269
FT /note="R->A: Reduced p38 alpha- and beta2-mediated
FT transcriptional activity; when associated with A-270."
FT /evidence="ECO:0000269|PubMed:10330143"
FT MUTAGEN 270
FT /note="K->A: Reduced p38 alpha- and beta2-mediated
FT transcriptional activity; when associated with A-269."
FT /evidence="ECO:0000269|PubMed:10330143"
FT MUTAGEN 273
FT /note="L->A: Reduced p38 alpha- and beta2-mediated
FT transcriptional activity; when associated with A-275."
FT /evidence="ECO:0000269|PubMed:10330143"
FT MUTAGEN 275
FT /note="V->A: Reduced p38 alpha- and beta2-mediated
FT transcriptional activity; when associated with A-273."
FT /evidence="ECO:0000269|PubMed:10330143"
FT MUTAGEN 277
FT /note="I->A: Reduced p38 alpha- and beta2-mediated
FT transcriptional activity; when associated with A-278."
FT /evidence="ECO:0000269|PubMed:10330143"
FT MUTAGEN 278
FT /note="P->A: Reduced p38 alpha- and beta2-mediated
FT transcriptional activity; when associated with A-277."
FT /evidence="ECO:0000269|PubMed:10330143"
FT MUTAGEN 312
FT /note="T->A: Greatly reduced p38-mediated phosphorylation.
FT Abolishes p38-mediated transcriptional activation; when
FT associated with A-319."
FT /evidence="ECO:0000269|PubMed:10849446,
FT ECO:0000269|PubMed:9858528"
FT MUTAGEN 319
FT /note="T->A: Greatly reduced p38-mediated phosphorylation.
FT Abolishes P38-mediated transcriptional activation; when
FT associated with A-312."
FT /evidence="ECO:0000269|PubMed:10849446,
FT ECO:0000269|PubMed:9858528"
FT MUTAGEN 355
FT /note="S->A: No effect on p38-mediated transcriptional
FT activity."
FT /evidence="ECO:0000269|PubMed:10849446,
FT ECO:0000269|PubMed:9858528"
FT MUTAGEN 387
FT /note="S->A: No effect on p38-mediated phosphorylation."
FT MUTAGEN 403
FT /note="K->R: Abolishes sumoylation. No change in
FT subcellular location nor in DNA binding. Loss of
FT transcriptional repression."
FT /evidence="ECO:0000269|PubMed:16371476,
FT ECO:0000269|PubMed:16563226"
FT MUTAGEN 408
FT /note="S->A: Loss of sumoylation."
FT /evidence="ECO:0000269|PubMed:12691662,
FT ECO:0000269|PubMed:16371476"
FT MUTAGEN 408
FT /note="S->D: Rescues sumoylation."
FT /evidence="ECO:0000269|PubMed:12691662,
FT ECO:0000269|PubMed:16371476"
FT MUTAGEN 453
FT /note="S->A: No effect on p38-mediated phosphorylation."
FT /evidence="ECO:0000269|PubMed:9858528"
FT MUTAGEN 479
FT /note="S->A: No effect on p38-mediated phosphorylation."
FT /evidence="ECO:0000269|PubMed:9858528"
FT CONFLICT 430
FT /note="Missing (in Ref. 4; AAB17195/AAB17196)"
FT /evidence="ECO:0000305"
FT HELIX 14..38
FT /evidence="ECO:0007829|PDB:1EGW"
FT STRAND 42..48
FT /evidence="ECO:0007829|PDB:1EGW"
FT TURN 50..52
FT /evidence="ECO:0007829|PDB:1C7U"
FT STRAND 54..60
FT /evidence="ECO:0007829|PDB:1EGW"
FT HELIX 62..71
FT /evidence="ECO:0007829|PDB:1EGW"
FT STRAND 77..80
FT /evidence="ECO:0007829|PDB:3KOV"
FT HELIX 81..90
FT /evidence="ECO:0007829|PDB:3P57"
FT MOD_RES Q02078-2:98
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES Q02078-4:98
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES Q02078-6:98
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES Q02078-7:30
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES Q02078-8:30
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
SQ SEQUENCE 507 AA; 54811 MW; 362BA4FBCC792CE2 CRC64;
MGRKKIQITR IMDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNS SNKLFQYAST
DMDKVLLKYT EYNEPHESRT NSDIVEALNK KEHRGCDSPD PDTSYVLTPH TEEKYKKINE
EFDNMMRNHK IAPGLPPQNF SMSVTVPVTS PNALSYTNPG SSLVSPSLAA SSTLTDSSML
SPPQTTLHRN VSPGAPQRPP STGNAGGMLS TTDLTVPNGA GSSPVGNGFV NSRASPNLIG
ATGANSLGKV MPTKSPPPPG GGNLGMNSRK PDLRVVIPPS SKGMMPPLSE EEELELNTQR
ISSSQATQPL ATPVVSVTTP SLPPQGLVYS AMPTAYNTDY SLTSADLSAL QGFNSPGMLS
LGQVSAWQQH HLGQAALSSL VAGGQLSQGS NLSINTNQNI SIKSEPISPP RDRMTPSGFQ
QQQQQQQQQQ PPPPPQPQPQ PPQPQPRQEM GRSPVDSLSS SSSSYDGSDR EDPRGDFHSP
IVLGRPPNTE DRESPSVKRM RMDAWVT
