MEF2A_RAT
ID MEF2A_RAT Reviewed; 495 AA.
AC Q2MJT0; Q66HD7;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 07-FEB-2006, sequence version 1.
DT 25-MAY-2022, entry version 107.
DE RecName: Full=Myocyte-specific enhancer factor 2A;
GN Name=Mef2a;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND FUNCTION.
RC STRAIN=Sprague-Dawley;
RX PubMed=17367767; DOI=10.1016/j.cardiores.2007.02.007;
RA Wang Y.-X., Qian L.-X., Liu D., Yao L.-L., Jiang Q., Yu Z., Gui Y.-H.,
RA Zhong T.-P., Song H.-Y.;
RT "Bone morphogenetic protein-2 acts upstream of myocyte-specific enhancer
RT factor 2a to control embryonic cardiac contractility.";
RL Cardiovasc. Res. 74:290-303(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 [3]
RP FUNCTION, PHOSPHORYLATION AT SER-400, SUMOYLATION AT LYS-395, ACETYLATION
RP AT LYS-395, AND MUTAGENESIS OF LYS-395 AND SER-400.
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 [4]
RP SUMOYLATION, AND FUNCTION.
RX PubMed=17855618; DOI=10.1523/jneurosci.0361-07.2007;
RA Shalizi A., Bilimoria P.M., Stegmueller J., Gaudilliere B., Yang Y.,
RA Shuai K., Bonni A.;
RT "PIASx is a MEF2 SUMO E3 ligase that promotes postsynaptic dendritic
RT morphogenesis.";
RL J. Neurosci. 27:10037-10046(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98; SER-235 AND SER-255, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:16484498, ECO:0000269|PubMed:17367767,
CC ECO:0000269|PubMed:17855618}.
CC -!- SUBUNIT: Binds DNA as a homo- or heterodimer (By similarity). Dimerizes
CC with MEF2D. Interacts with HDAC7. Interacts with PIAS1; the interaction
CC enhances sumoylation. Interacts with HDAC4, HDAC9 and SLC2A4RG.
CC Interacts (via the N-terminal) with MAPK7; the interaction results in
CC the phosphorylation and transcriptional activity of MEF2A (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00251,
CC ECO:0000269|PubMed:17367767}.
CC -!- PTM: Constitutive phosphorylation on Ser-400 promotes Lys-395
CC sumoylation thus preventing acetylation at this site. Dephosphorylation
CC on Ser-400 by PPP3CA upon neuron depolarization promotes a switch from
CC sumoylation to acetylation on residue Lys-395 leading to inhibition of
CC dendrite claw differentiation. Phosphorylation on Thr-304 and Thr-311
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-400 by CDK5 induced by neurotoxicity inhibits
CC MEF2A transcriptional activation leading to apoptosis of cortical
CC neurons. Phosphorylation on Thr-304, Thr-311 and Ser-347 can be induced
CC by EGF (By similarity). {ECO:0000250}.
CC -!- PTM: Sumoylation on Lys-395 is enhanced by PIAS1 and represses
CC transcriptional activity. Phosphorylation on Ser-400 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-395 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, ECO:0000269|PubMed:16484498}.
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 (By
CC similarity). {ECO:0000250}.
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DR EMBL; DQ323505; ABC55063.1; -; mRNA.
DR EMBL; BC081907; AAH81907.1; -; mRNA.
DR RefSeq; NP_001014057.1; NM_001014035.1.
DR RefSeq; XP_017444797.1; XM_017589308.1.
DR AlphaFoldDB; Q2MJT0; -.
DR SMR; Q2MJT0; -.
DR MINT; Q2MJT0; -.
DR STRING; 10116.ENSRNOP00000065122; -.
DR iPTMnet; Q2MJT0; -.
DR PhosphoSitePlus; Q2MJT0; -.
DR PaxDb; Q2MJT0; -.
DR GeneID; 309957; -.
DR KEGG; rno:309957; -.
DR CTD; 4205; -.
DR RGD; 1359360; Mef2a.
DR eggNOG; KOG0014; Eukaryota.
DR InParanoid; Q2MJT0; -.
DR OrthoDB; 729387at2759; -.
DR PhylomeDB; Q2MJT0; -.
DR Reactome; R-RNO-525793; Myogenesis.
DR PRO; PR:Q2MJT0; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0000785; C:chromatin; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0035035; F:histone acetyltransferase binding; ISS:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0046332; F:SMAD binding; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0061337; P:cardiac conduction; ISO:RGD.
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:0071333; P:cellular response to glucose stimulus; IEP:RGD.
DR GO; GO:0048813; P:dendrite morphogenesis; IMP:UniProtKB.
DR GO; GO:0070375; P:ERK5 cascade; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0000165; P:MAPK cascade; ISS:UniProtKB.
DR GO; GO:0000002; P:mitochondrial genome maintenance; ISO:RGD.
DR GO; GO:0048311; P:mitochondrion distribution; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0046326; P:positive regulation of glucose import; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0006351; P:transcription, DNA-templated; ISO:RGD.
DR GO; GO:0055005; P:ventricular cardiac myofibril assembly; ISO:RGD.
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; Apoptosis; Developmental protein; Differentiation;
KW DNA-binding; Isopeptide bond; Neurogenesis; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..495
FT /note="Myocyte-specific enhancer factor 2A"
FT /id="PRO_0000366970"
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 175..225
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 242..271
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 266..283
FT /note="Required for interaction with MAPKs"
FT /evidence="ECO:0000250"
FT REGION 382..495
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 195..218
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 382..397
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 420..435
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 436..454
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 213..214
FT /note="Cleavage"
FT /evidence="ECO:0000305"
FT SITE 454..455
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:22673903"
FT MOD_RES 235
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 249
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT MOD_RES 255
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 304
FT /note="Phosphothreonine; by MAPK7 and MAPK14"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT MOD_RES 311
FT /note="Phosphothreonine; by MAPK7 and MAPK14"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT MOD_RES 347
FT /note="Phosphoserine; by MAPK7"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT MOD_RES 395
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:16484498"
FT MOD_RES 400
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000269|PubMed:16484498"
FT MOD_RES 407
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q60929"
FT MOD_RES 441
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT CROSSLNK 395
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT MUTAGEN 395
FT /note="K->R: Abolishes sumoylation."
FT /evidence="ECO:0000269|PubMed:16484498"
FT MUTAGEN 400
FT /note="S->A: Abolishes K-395 sumoylation. Enhances K-395
FT acetylation. Enhances transcriptional activity."
FT /evidence="ECO:0000269|PubMed:16484498"
FT CONFLICT 223
FT /note="G -> S (in Ref. 2; AAH81907)"
FT /evidence="ECO:0000305"
FT CONFLICT 231
FT /note="D -> N (in Ref. 2; AAH81907)"
FT /evidence="ECO:0000305"
FT CONFLICT 396
FT /note="T -> S (in Ref. 2; AAH81907)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 495 AA; 53254 MW; 8ED69528402E613E CRC64;
MGRKKIQITR IMDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNS SNKLFQYAST
DMDKVLLKYT EYNEPHESRT NSDIVEALNK KEHRGCDSPD PDTSYVLTPH TEEKYKKINE
EFDNMMRNHK IAPGLPPQNF SMSVTVPVTS PNALSYTNPG SSLVSPSLAA SSTLAESSML
SPPPATLHRN VSPGAPQRPP STGSAGGMLS TTDLTVPNGA GNGPVGNGFV DSRASPNLIG
NTGANSVGKV MPTKSPPPPG GGSVGMNSRK PDLRVVIPPS SKGMMPPLNA QRISSSQATQ
PLATPVVSVT TPSLPPQGLV YSAMPTAYNT DYSLTSADLS ALQGFTSPGM LSLGQASAWQ
QHHLGQAALS SLVAGGQLSQ GSNLSINTNQ NINIKTEPIS PPRDRMTPSG FQQQQQQQPQ
QQPPPQPPQP QPQPRQEMGR SPVDSLSSSS SSYDGSDRED PRGDFHSPIV LGRPPNAEDR
ESPSVKRMRM DTWVT
