MEF2D_RAT
ID MEF2D_RAT Reviewed; 507 AA.
AC O89038; Q66HL8;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Myocyte-specific enhancer factor 2D;
GN Name=Mef2d;
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], AND INTERACTION WITH MAPK7.
RC STRAIN=Wistar; TISSUE=Heart;
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 [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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98; SER-106; SER-121;
RP SER-180; SER-231 AND SER-251, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 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}.
CC -!- SUBUNIT: Forms a complex with class II HDACs in undifferentiating
CC cells. On myogenic differentiation, HDACs are released into the
CC cytoplasm allowing MEF2s to interact with other proteins for
CC activation. Interacts with HDAC4 (in undifferentiating cells); the
CC interaction translocates MEF2D to nuclear dots (By similarity). Forms a
CC heterodimer with MEF2A (By similarity). Interacts with MAPK7; the
CC interaction phosphorylates but does not activate MEF2D
CC (PubMed:9753748). Interacts with MYOG (By similarity). Interacts with
CC CCAR2 and HDAC3 (By similarity). {ECO:0000250|UniProtKB:Q14814,
CC ECO:0000250|UniProtKB:Q63943, ECO:0000269|PubMed:9753748}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Note=Translocated by HDAC4 to nuclear
CC dots. {ECO:0000250}.
CC -!- PTM: Phosphorylated on Ser-430 by CDK5 is required for Lys-425
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 (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Acetylated on Lys-425 by CREBBP. Acetylated by EP300. Deacetylated
CC by SIRT1 and HDAC3 (By similarity). {ECO:0000250|UniProtKB:Q14814}.
CC -!- PTM: Sumoylated on Lys-425 with SUMO2 but not SUMO1; which inhibits
CC transcriptional activity and myogenic activity. Desumoylated by SENP3
CC (By similarity). {ECO:0000250}.
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DR EMBL; AJ005425; CAA06531.1; -; mRNA.
DR EMBL; BC081790; AAH81790.1; -; mRNA.
DR RefSeq; NP_110487.2; NM_030860.2.
DR RefSeq; XP_017446620.1; XM_017591131.1.
DR AlphaFoldDB; O89038; -.
DR SMR; O89038; -.
DR BioGRID; 249515; 5.
DR STRING; 10116.ENSRNOP00000041061; -.
DR iPTMnet; O89038; -.
DR PhosphoSitePlus; O89038; -.
DR PaxDb; O89038; -.
DR PRIDE; O89038; -.
DR GeneID; 81518; -.
DR KEGG; rno:81518; -.
DR CTD; 4209; -.
DR RGD; 621489; Mef2d.
DR eggNOG; KOG0014; Eukaryota.
DR InParanoid; O89038; -.
DR OrthoDB; 729387at2759; -.
DR PhylomeDB; O89038; -.
DR Reactome; R-RNO-525793; Myogenesis.
DR PRO; PR:O89038; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA: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; ISO:RGD.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; 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; ISO:RGD.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0007512; P:adult heart development; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0001958; P:endochondral ossification; ISO:RGD.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0001649; P:osteoblast differentiation; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; ISO:RGD.
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:0035914; P:skeletal muscle cell differentiation; 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..507
FT /note="Myocyte-specific enhancer factor 2D"
FT /id="PRO_0000366974"
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..267
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 357..392
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 423..507
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 362..390
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 433..448
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 106
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 110
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63943"
FT MOD_RES 121
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 180
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
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:22673903"
FT MOD_RES 245
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q14814"
FT MOD_RES 251
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 425
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q14814"
FT MOD_RES 430
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14814"
FT CROSSLNK 425
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CONFLICT 208
FT /note="R -> G (in Ref. 2; AAH81790)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 507 AA; 54368 MW; 303D4A865805FA41 CRC64;
MGRKKIQIQR ITDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNH SNKLFQYAST
DMDKVLLKYT EYNEPHESRT NADIIETLRK KGFNGCDSPE PDGEDSLEQS PLLEDKYRRA
SEELDGLFRR YGSSVPAPNF AMPVTVPVSN QSSMQFSNPS SSLVTPSLVT SSLTDPRLLS
PQQPALQRNS VSPGLPQRPA SAGAMLGRDL NSANGACPNP VGNGYVSARA SPGLLPVANG
NGLNKVIPAK SPPPPTHNTQ LGAPSRKPDL RVITSQGGKG LMHHLNNAQR LGVSQSTHSL
TTPVVSVATP SLLSQGLPFS SMPTAYNTDY QLPSAELSSL PAFSSPAGLA LGNVTAWQQP
QQPQQPQPPQ PPQSQPQPPQ PQPQQPPQQQ PHLVPVSLSN LIPGSPLPHV GAALTVTTHP
HISIKSEPVS PSRERSPAPP PPAVFPAARP EPGEGLSSPA GGSYETGDRD DGRGDFGPTL
GLLRPAPEPE AEGSAVKRMR LDTWTLK
