MEF2D_HUMAN
ID MEF2D_HUMAN Reviewed; 521 AA.
AC Q14814; D3DVC0; Q14815; Q5T9U5; Q5T9U6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Myocyte-specific enhancer factor 2D;
GN Name=MEF2D;
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 [GENOMIC DNA / MRNA] (ISOFORMS MEF2D00; MEF2D0B;
RP MEF2DA'0; MEF2DA'B; MEF2DA0 AND MEF2DAB).
RC TISSUE=Myocardium;
RX PubMed=8269842; DOI=10.1242/dev.118.4.1095;
RA Breitbart R.E., Liang C.-S., Smoot L.B., Laheru D.A., Mahdavi V.,
RA Nadal-Ginard B.;
RT "A fourth human MEF2 transcription factor, hMEF2D, is an early marker of
RT the myogenic lineage.";
RL Development 118:1095-1106(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS MEF2DA0 AND MEF2DAB).
RC TISSUE=Eye, and Testis;
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 [5]
RP HETERODIMERIZATION.
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 [6]
RP INTERACTION WITH HDAC4.
RX PubMed=10523670; DOI=10.1128/mcb.19.11.7816;
RA Wang A.H., Bertos N.R., Vezmar M., Pelletier N., Crosato M., Heng H.H.,
RA Th'ng J., Han J., Yang X.-J.;
RT "HDAC4, a human histone deacetylase related to yeast HDA1, is a
RT transcriptional corepressor.";
RL Mol. Cell. Biol. 19:7816-7827(1999).
RN [7]
RP PHOSPHORYLATION AT SER-180, FUNCTION, AND MUTAGENESIS OF SER-180 AND
RP SER-437.
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 [8]
RP PHOSPHORYLATION BY CAMK4.
RX PubMed=10617605; DOI=10.1074/jbc.275.1.197;
RA Blaeser F., Ho N., Prywes R., Chatila T.A.;
RT "Ca(2+)-dependent gene expression mediated by MEF2 transcription factors.";
RL J. Biol. Chem. 275:197-209(2000).
RN [9]
RP PROTEOLYTIC PROCESSING AT ASP-288, FUNCTION, AND MUTAGENESIS OF ASP-288.
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 [10]
RP PHOSPHORYLATION AT SER-444, FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS
RP OF SER-444.
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 [11]
RP FUNCTION OF BETA DOMAIN, AND MUTAGENESIS OF THR-286; GLU-287; ASP-288;
RP HIS-289 AND ASP-291.
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 [12]
RP PROTEOLYTIC PROCESSING, PHOSPHORYLATION AT SER-444, AND MUTAGENESIS OF
RP SER-444.
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 [13]
RP SUMOYLATION AT LYS-439, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=15743823; DOI=10.1128/mcb.25.6.2273-2287.2005;
RA Gregoire S., Yang X.-J.;
RT "Association with class IIa histone deacetylases upregulates the
RT sumoylation of MEF2 transcription factors.";
RL Mol. Cell. Biol. 25:2273-2287(2005).
RN [14]
RP SUMOYLATION AT LYS-439, ACETYLATION AT LYS-439, DEACETYLATION, AND
RP MUTAGENESIS OF ILE-438 AND LYS-439.
RX PubMed=16166628; DOI=10.1128/mcb.25.19.8456-8464.2005;
RA Zhao X., Sternsdorf T., Bolger T.A., Evans R.M., Yao T.-P.;
RT "Regulation of MEF2 by histone deacetylase 4- and SIRT1 deacetylase-
RT mediated lysine modifications.";
RL Mol. Cell. Biol. 25:8456-8464(2005).
RN [15]
RP ACETYLATION.
RX PubMed=15831463; DOI=10.1128/mcb.25.9.3575-3582.2005;
RA Ma K., Chan J.K., Zhu G., Wu Z.;
RT "Myocyte enhancer factor 2 acetylation by p300 enhances its DNA binding
RT activity, transcriptional activity, and myogenic differentiation.";
RL Mol. Cell. Biol. 25:3575-3582(2005).
RN [16]
RP SUMOYLATION AT LYS-439, PHOSPHORYLATION AT SER-444, AND MUTAGENESIS OF
RP LYS-439 AND SER-444.
RX PubMed=16356933; DOI=10.1074/jbc.m509471200;
RA Gregoire S., Tremblay A.M., Xiao L., Yang Q., Ma K., Nie J., Mao Z., Wu Z.,
RA Giguere V., Yang X.-J.;
RT "Control of MEF2 transcriptional activity by coordinated phosphorylation
RT and sumoylation.";
RL J. Biol. Chem. 281:4423-4433(2006).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-180, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-180, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231 AND SER-251, AND
RP 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 [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-245, 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 [22]
RP INTERACTION WITH CCAR2 AND HDAC3, ACETYLATION, AND DEACETYLATION.
RX PubMed=21030595; DOI=10.1074/jbc.m110.153270;
RA Chini C.C., Escande C., Nin V., Chini E.N.;
RT "HDAC3 is negatively regulated by the nuclear protein DBC1.";
RL J. Biol. Chem. 285:40830-40837(2010).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-180, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [24]
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 [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-121; SER-180; SER-231 AND
RP SER-251, AND 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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-251, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Transcriptional activator which binds specifically to the
CC MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific,
CC growth factor- and stress-induced genes. Mediates cellular functions
CC not only in skeletal and cardiac muscle development, but also in
CC neuronal differentiation and survival. Plays diverse roles in the
CC control of cell growth, survival and apoptosis via p38 MAPK signaling
CC in muscle-specific and/or growth factor-related transcription. Plays a
CC critical role in the regulation of neuronal apoptosis (By similarity).
CC {ECO:0000250, ECO:0000269|PubMed:10849446, ECO:0000269|PubMed:11904443,
CC ECO:0000269|PubMed:12691662, ECO:0000269|PubMed:15743823,
CC ECO:0000269|PubMed:15834131}.
CC -!- SUBUNIT: Interacts with MYOG (By similarity). Forms a complex with
CC class II HDACs in undifferentiating cells. On myogenic differentiation,
CC HDACs are released into the cytoplasm allowing MEF2s to interact with
CC other proteins for activation. Interacts with HDAC4 (in
CC undifferentiating cells); the interaction translocates MEF2D to nuclear
CC dots. Forms a heterodimer with MEF2A. Interacts with MAPK7; the
CC interaction phosphorylates but does not activate MEF2D (By similarity).
CC Interacts with CCAR2 and HDAC3. {ECO:0000250|UniProtKB:O89038,
CC ECO:0000250|UniProtKB:Q63943, ECO:0000269|PubMed:10523670,
CC ECO:0000269|PubMed:21030595}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00251,
CC ECO:0000269|PubMed:12691662, ECO:0000269|PubMed:15743823}.
CC Note=Translocated by HDAC4 to nuclear dots.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=MEF2DAB;
CC IsoId=Q14814-1; Sequence=Displayed;
CC Name=MEF2DA'B;
CC IsoId=Q14814-2; Sequence=VSP_006250;
CC Name=MEF2D0B;
CC IsoId=Q14814-3; Sequence=VSP_006251;
CC Name=MEF2DA0;
CC IsoId=Q14814-4; Sequence=VSP_006252;
CC Name=MEF2DA'0;
CC IsoId=Q14814-5; Sequence=VSP_006250, VSP_006252;
CC Name=MEF2D00;
CC IsoId=Q14814-6; Sequence=VSP_006251, VSP_006252;
CC -!- DEVELOPMENTAL STAGE: Present in myotubes and also in undifferentiated
CC myoblasts.
CC -!- DOMAIN: The beta domain, missing in a number of isoforms, is required
CC for enhancement of transcriptional activity.
CC -!- PTM: Phosphorylated on Ser-444 by CDK5 is required for Lys-439
CC sumoylation and inhibits transcriptional activity. In neurons, enhanced
CC CDK5 activity induced by neurotoxins promotes caspase 3-mediated
CC cleavage leading to neuron apoptosis. Phosphorylation on Ser-180 can be
CC enhanced by EGF. Phosphorylated and activated by CaMK4.
CC {ECO:0000269|PubMed:10617605, ECO:0000269|PubMed:10849446,
CC ECO:0000269|PubMed:11904443, ECO:0000269|PubMed:12691662,
CC ECO:0000269|PubMed:15743823, ECO:0000269|PubMed:15888658,
CC ECO:0000269|PubMed:16166628, ECO:0000269|PubMed:16356933}.
CC -!- PTM: Acetylated on Lys-439 by CREBBP. Acetylated by EP300. Deacetylated
CC by SIRT1 and HDAC3. {ECO:0000269|PubMed:15831463,
CC ECO:0000269|PubMed:16166628, ECO:0000269|PubMed:21030595}.
CC -!- PTM: Sumoylated on Lys-439 with SUMO2 but not SUMO1; which inhibits
CC transcriptional activity and myogenic activity. Desumoylated by SENP3.
CC {ECO:0000269|PubMed:15743823, ECO:0000269|PubMed:16166628,
CC ECO:0000269|PubMed:16356933}.
CC -!- PTM: Proteolytically cleaved in cerebellar granule neurons on several
CC sites by caspase 7 following neurotoxicity. Preferentially cleaves the
CC CDK5-mediated hyperphosphorylated form which leads to neuron apoptosis
CC and transcriptional inactivation (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the MEF2 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MEF2DID43636ch1q22.html";
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DR EMBL; L16794; AAA93194.1; -; mRNA.
DR EMBL; L16795; AAA59579.1; -; Genomic_DNA.
DR EMBL; AL139412; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW52948.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52952.1; -; Genomic_DNA.
DR EMBL; BC040949; AAH40949.1; -; mRNA.
DR EMBL; BC054520; AAH54520.1; -; mRNA.
DR CCDS; CCDS1143.1; -. [Q14814-1]
DR CCDS; CCDS60304.1; -. [Q14814-4]
DR PIR; I53124; I53124.
DR RefSeq; NP_001258558.1; NM_001271629.1. [Q14814-4]
DR RefSeq; NP_005911.1; NM_005920.3. [Q14814-1]
DR RefSeq; XP_005245226.1; XM_005245169.4. [Q14814-1]
DR RefSeq; XP_005245227.1; XM_005245170.3. [Q14814-1]
DR RefSeq; XP_006711393.1; XM_006711330.3. [Q14814-1]
DR RefSeq; XP_006711395.1; XM_006711332.3. [Q14814-2]
DR RefSeq; XP_006711396.1; XM_006711333.2. [Q14814-4]
DR RefSeq; XP_006711397.1; XM_006711334.3. [Q14814-5]
DR RefSeq; XP_011507871.1; XM_011509569.2. [Q14814-1]
DR RefSeq; XP_016856803.1; XM_017001314.1. [Q14814-4]
DR RefSeq; XP_016856804.1; XM_017001315.1. [Q14814-4]
DR AlphaFoldDB; Q14814; -.
DR SMR; Q14814; -.
DR BioGRID; 110373; 70.
DR ELM; Q14814; -.
DR IntAct; Q14814; 36.
DR MINT; Q14814; -.
DR STRING; 9606.ENSP00000271555; -.
DR BindingDB; Q14814; -.
DR GlyConnect; 2862; 1 O-Linked glycan (1 site).
DR GlyGen; Q14814; 18 sites, 2 O-linked glycans (18 sites).
DR iPTMnet; Q14814; -.
DR PhosphoSitePlus; Q14814; -.
DR BioMuta; MEF2D; -.
DR DMDM; 2500876; -.
DR EPD; Q14814; -.
DR jPOST; Q14814; -.
DR MassIVE; Q14814; -.
DR MaxQB; Q14814; -.
DR PaxDb; Q14814; -.
DR PeptideAtlas; Q14814; -.
DR PRIDE; Q14814; -.
DR ProteomicsDB; 60190; -. [Q14814-1]
DR ProteomicsDB; 60191; -. [Q14814-2]
DR ProteomicsDB; 60192; -. [Q14814-3]
DR ProteomicsDB; 60193; -. [Q14814-4]
DR ProteomicsDB; 60194; -. [Q14814-5]
DR ProteomicsDB; 60195; -. [Q14814-6]
DR Antibodypedia; 1437; 495 antibodies from 35 providers.
DR DNASU; 4209; -.
DR Ensembl; ENST00000348159.9; ENSP00000271555.5; ENSG00000116604.19. [Q14814-1]
DR Ensembl; ENST00000360595.7; ENSP00000353803.3; ENSG00000116604.19. [Q14814-4]
DR Ensembl; ENST00000464356.6; ENSP00000476788.1; ENSG00000116604.19. [Q14814-5]
DR GeneID; 4209; -.
DR KEGG; hsa:4209; -.
DR MANE-Select; ENST00000348159.9; ENSP00000271555.5; NM_005920.4; NP_005911.1.
DR UCSC; uc001fpb.5; human. [Q14814-1]
DR CTD; 4209; -.
DR DisGeNET; 4209; -.
DR GeneCards; MEF2D; -.
DR HGNC; HGNC:6997; MEF2D.
DR HPA; ENSG00000116604; Tissue enhanced (skeletal).
DR MIM; 600663; gene.
DR neXtProt; NX_Q14814; -.
DR OpenTargets; ENSG00000116604; -.
DR PharmGKB; PA30735; -.
DR VEuPathDB; HostDB:ENSG00000116604; -.
DR eggNOG; KOG0014; Eukaryota.
DR GeneTree; ENSGT00940000159463; -.
DR HOGENOM; CLU_022902_4_0_1; -.
DR InParanoid; Q14814; -.
DR OMA; NISAWHQ; -.
DR OrthoDB; 729387at2759; -.
DR PhylomeDB; Q14814; -.
DR TreeFam; TF314067; -.
DR PathwayCommons; Q14814; -.
DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis.
DR Reactome; R-HSA-400253; Circadian Clock.
DR Reactome; R-HSA-525793; Myogenesis.
DR Reactome; R-HSA-9031628; NGF-stimulated transcription.
DR Reactome; R-HSA-9707616; Heme signaling.
DR SignaLink; Q14814; -.
DR SIGNOR; Q14814; -.
DR BioGRID-ORCS; 4209; 47 hits in 1100 CRISPR screens.
DR ChiTaRS; MEF2D; human.
DR GeneWiki; MEF2D; -.
DR GenomeRNAi; 4209; -.
DR Pharos; Q14814; Tbio.
DR PRO; PR:Q14814; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q14814; protein.
DR Bgee; ENSG00000116604; Expressed in hindlimb stylopod muscle and 190 other tissues.
DR ExpressionAtlas; Q14814; baseline and differential.
DR Genevisible; Q14814; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; NAS:ProtInc.
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:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
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:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0007512; P:adult heart development; IEP:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0002062; P:chondrocyte differentiation; IEA:Ensembl.
DR GO; GO:0001958; P:endochondral ossification; IEA:Ensembl.
DR GO; GO:0007517; P:muscle organ development; TAS:ProtInc.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IGI:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; IEA:Ensembl.
DR CDD; cd00265; MADS_MEF2_like; 1.
DR Gene3D; 3.40.1810.10; -; 1.
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 Acetylation; Activator; Alternative splicing; Apoptosis;
KW Developmental protein; Differentiation; DNA-binding; Isopeptide bond;
KW Neurogenesis; Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..521
FT /note="Myocyte-specific enhancer factor 2D"
FT /id="PRO_0000199435"
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 174..207
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 244..266
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 286..292
FT /note="Beta domain"
FT REGION 357..407
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 437..521
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 174..196
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 371..398
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 447..462
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 288..289
FT /note="Cleavage"
FT /evidence="ECO:0000305"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63943"
FT MOD_RES 106
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63943"
FT MOD_RES 110
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63943"
FT MOD_RES 121
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:10617605,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 180
FT /note="Phosphoserine; by MAPK7"
FT /evidence="ECO:0000269|PubMed:10849446,
FT ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 190
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q63943"
FT MOD_RES 231
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 245
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 251
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 439
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:16166628"
FT MOD_RES 444
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12691662,
FT ECO:0000269|PubMed:15888658, ECO:0000269|PubMed:16356933"
FT CROSSLNK 439
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT VAR_SEQ 87..132
FT /note="Missing (in isoform MEF2D0B and isoform MEF2D00)"
FT /evidence="ECO:0000303|PubMed:8269842"
FT /id="VSP_006251"
FT VAR_SEQ 87..132
FT /note="TLRKKGFNGCDSPEPDGEDSLEQSPLLEDKYRRASEELDGLFRRYG -> AL
FT HKKHRECESPEVDEVFALTPQTEEKYKKIDEEFDKMMQSYRLA (in isoform
FT MEF2DA'B and isoform MEF2DA'0)"
FT /evidence="ECO:0000303|PubMed:8269842"
FT /id="VSP_006250"
FT VAR_SEQ 286..292
FT /note="Missing (in isoform MEF2DA0, isoform MEF2DA'0 and
FT isoform MEF2D00)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8269842"
FT /id="VSP_006252"
FT VARIANT 434
FT /note="P -> S (in dbSNP:rs2274315)"
FT /id="VAR_022155"
FT MUTAGEN 180
FT /note="S->A: Abolishes MAPK7- and EGF-mediated
FT transcriptional activation."
FT /evidence="ECO:0000269|PubMed:10849446"
FT MUTAGEN 286
FT /note="T->A: Same transcriptional activity as for isoforms
FT with beta domain."
FT /evidence="ECO:0000269|PubMed:15834131"
FT MUTAGEN 287
FT /note="E->Q: Abolishes transcriptional activity; when
FT associated with N-288 and N-291."
FT /evidence="ECO:0000269|PubMed:15834131"
FT MUTAGEN 288
FT /note="D->A: Abolishes cleavage by caspase 7."
FT /evidence="ECO:0000269|PubMed:11904443,
FT ECO:0000269|PubMed:15834131"
FT MUTAGEN 288
FT /note="D->N: Abolishes transcriptional activity; when
FT associated with Q-287 and N-291."
FT /evidence="ECO:0000269|PubMed:11904443,
FT ECO:0000269|PubMed:15834131"
FT MUTAGEN 289
FT /note="H->A: Same transcriptional activity as for isoforms
FT with beta domain."
FT /evidence="ECO:0000269|PubMed:15834131"
FT MUTAGEN 291
FT /note="D->N: Abolishes transcriptional activity; when
FT associated with Q-287 and N-288."
FT /evidence="ECO:0000269|PubMed:15834131"
FT MUTAGEN 437
FT /note="S->A: No effect on MAPK7- or EGF-mediated
FT transcriptional activity."
FT /evidence="ECO:0000269|PubMed:10849446"
FT MUTAGEN 438
FT /note="I->A: Abolishes K-439 sumoylation."
FT /evidence="ECO:0000269|PubMed:16166628"
FT MUTAGEN 439
FT /note="K->R: Abolishes sumoylation and acetylation."
FT /evidence="ECO:0000269|PubMed:16166628,
FT ECO:0000269|PubMed:16356933"
FT MUTAGEN 444
FT /note="S->A: Abolishes K-439 sumoylation. Reduced
FT neurotoxin-induced apoptosis of neuronal cells. More
FT resistant to degradation."
FT /evidence="ECO:0000269|PubMed:12691662,
FT ECO:0000269|PubMed:15888658, ECO:0000269|PubMed:16356933"
FT MUTAGEN 444
FT /note="S->E: No effect on K-439 sumoylation."
FT /evidence="ECO:0000269|PubMed:12691662,
FT ECO:0000269|PubMed:15888658, ECO:0000269|PubMed:16356933"
SQ SEQUENCE 521 AA; 55938 MW; 5C9790AD598619BA CRC64;
MGRKKIQIQR ITDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNH SNKLFQYAST
DMDKVLLKYT EYNEPHESRT NADIIETLRK KGFNGCDSPE PDGEDSLEQS PLLEDKYRRA
SEELDGLFRR YGSTVPAPNF AMPVTVPVSN QSSLQFSNPS GSLVTPSLVT SSLTDPRLLS
PQQPALQRNS VSPGLPQRPA SAGAMLGGDL NSANGACPSP VGNGYVSARA SPGLLPVANG
NSLNKVIPAK SPPPPTHSTQ LGAPSRKPDL RVITSQAGKG LMHHLTEDHL DLNNAQRLGV
SQSTHSLTTP VVSVATPSLL SQGLPFSSMP TAYNTDYQLT SAELSSLPAF SSPGGLSLGN
VTAWQQPQQP QQPQQPQPPQ QQPPQPQQPQ PQQPQQPQQP PQQQSHLVPV SLSNLIPGSP
LPHVGAALTV TTHPHISIKS EPVSPSRERS PAPPPPAVFP AARPEPGDGL SSPAGGSYET
GDRDDGRGDF GPTLGLLRPA PEPEAEGSAV KRMRLDTWTL K
