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Protein

Myocyte-specific enhancer factor 2C

Gene

Mef2c

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Transcription activator which binds specifically to the MEF2 element present in the regulatory regions of many muscle-specific genes (PubMed:15862299). Controls cardiac morphogenesis and myogenesis, and is also involved in vascular development. Plays an essential role in hippocampal-dependent learning and memory by suppressing the number of excitatory synapses and thus regulating basal and evoked synaptic transmission. Crucial for normal neuronal development, distribution, and electrical activity in the neocortex. Necessary for proper development of megakaryocytes and platelets and for bone marrow B-lymphopoiesis. Required for B-cell survival and proliferation in response to BCR stimulation, efficient IgG1 antibody responses to T-cell-dependent antigens and for normal induction of germinal center B-cells. May also be involved in neurogenesis and in the development of cortical architecture (By similarity).By similarity1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi58 – 86Mef2-typeSequence analysisAdd BLAST29

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding
Biological processApoptosis, Differentiation, Neurogenesis, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-RNO-375170 CDO in myogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Myocyte-specific enhancer factor 2CCurated
Alternative name(s):
Myocyte enhancer factor 2CImported
Gene namesi
Name:Mef2cImported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 2

Organism-specific databases

RGDi1563119 Mef2c

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004418231 – 473Myocyte-specific enhancer factor 2CAdd BLAST473

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei4N6-acetyllysineBy similarity1
Modified residuei59Phosphoserine; by CK2By similarity1
Modified residuei98PhosphoserineCombined sources1
Modified residuei106PhosphoserineBy similarity1
Modified residuei110PhosphoserineCombined sources1
Modified residuei116N6-acetyllysineBy similarity1
Modified residuei119N6-acetyllysineBy similarity1
Modified residuei222PhosphoserineCombined sources1
Modified residuei228PhosphoserineBy similarity1
Modified residuei234N6-acetyllysineBy similarity1
Modified residuei239N6-acetyllysineBy similarity1
Modified residuei240PhosphoserineCombined sources1
Modified residuei252N6-acetyllysineBy similarity1
Modified residuei264N6-acetyllysineBy similarity1
Modified residuei293Phosphothreonine; by MAPK14By similarity1
Modified residuei300Phosphothreonine; by MAPK14By similarity1
Cross-linki391Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei396Phosphoserine; by CDK5By similarity1
Modified residuei419Phosphoserine; by MAPK7By similarity1
Modified residuei445PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated on Ser-59; which enhances DNA binding activity. Phosphorylated on Ser-396; which is required for Lys-391 sumoylation and inhibits transcriptional activity.By similarity
Acetylated by p300 on several sites in diffentiating myocytes. Acetylation on Lys-4 increases DNA binding and transactivation.By similarity
Sumoylated on Lys-391 with SUMO2 but not SUMO1; which represses transcriptional activity.By similarity
Proteolytically cleaved in cerebellar granule neurons on several sites by caspase 3 and caspase 7 following neurotoxicity. Preferentially cleaves the CDK5-mediated hyperphosphorylated form which leads to neuron apoptosis and transcriptional inactivation.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei432 – 433CleavageBy similarity2

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiA0A096MJY4

Expressioni

Tissue specificityi

Expressed in the heart (PubMed:15862299). Expressed in cardiac myocytes (at protein level) (PubMed:15862299).1 Publication

Gene expression databases

BgeeiENSRNOG00000033134
ExpressionAtlasiA0A096MJY4 baseline and differential

Interactioni

Subunit structurei

Forms a complex with class II HDACs in undifferentiating cells. On myogenic differentiation, HDACs are released into the cytoplasm allowing MEF2s to interact with other proteins for activation. Interacts with EP300 in differentiating cells; the interaction acetylates MEF2C leading to increased DNA binding and activation. Interacts with HDAC7 and CARM1. Interacts with HDAC4 and HDAC9; the interaction with HDACs represses transcriptional activity. Interacts with LPIN1. Interacts with MYOCD. Interacts with AKAP13. Interacts with FOXK1; the interaction inhibits MEF2C transactivation activity (By similarity). Interacts (via N-terminus) with HABP4; this interaction decreases DNA-binding activity of MEF2C in myocardial cells in response to mechanical stress (PubMed:15862299).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000046667

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 61MADS-boxPROSITE-ProRule annotationAdd BLAST61

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni271 – 278Beta domainBy similarity8
Regioni368 – 399Transcription repressorBy similarityAdd BLAST32

Domaini

The beta domain is required for enhancement of transcriptional activity.By similarity

Sequence similaritiesi

Belongs to the MEF2 family.Curated

Phylogenomic databases

eggNOGiKOG0014 Eukaryota
COG5068 LUCA
GeneTreeiENSGT00390000011828
KOiK04454
OMAiHLVMPNS
OrthoDBiEOG091G05BY

Family and domain databases

CDDicd00265 MADS_MEF2_like, 1 hit
Gene3Di3.40.1810.10, 1 hit
InterProiView protein in InterPro
IPR022102 HJURP_C
IPR033896 MADS_MEF2-like
IPR002100 TF_MADSbox
IPR036879 TF_MADSbox_sf
PfamiView protein in Pfam
PF12347 HJURP_C, 1 hit
PF00319 SRF-TF, 1 hit
PRINTSiPR00404 MADSDOMAIN
SMARTiView protein in SMART
SM00432 MADS, 1 hit
SUPFAMiSSF55455 SSF55455, 1 hit
PROSITEiView protein in PROSITE
PS00350 MADS_BOX_1, 1 hit
PS50066 MADS_BOX_2, 1 hit

Sequencei

Sequence statusi: Complete.

A0A096MJY4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRKKIQITR IMDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNS
60 70 80 90 100
TNKLFQYAST DMDKVLLKYT EYNEPHESRT NSDIVETLRK KGLNGCDSPD
110 120 130 140 150
PDADDSVGHS PESEDKYRKI NEDIDLMISR QRLCAVPPPN FEMPVTIPVS
160 170 180 190 200
SHNSLVYSNP VSSLGNPNLL PLAHPSLQRN SMSPGVTHRP PSAGNTGGLM
210 220 230 240 250
GGDLTSGAGT SAGNGYGNPR NSPGLLVSPG NLNKNIQAKS PPPMNLGMNN
260 270 280 290 300
RKPDLRVLIP PGSKNTMPSV SEDVDLLLNQ RINNSQSAQS LATPVVSVAT
310 320 330 340 350
PTLPGQGMGG YPSAISTTYG TEYSLSSADL SSLSGFNTAS ALHLGSVTGW
360 370 380 390 400
QQQHLHNMPP SALSQLGACT STHLSQSSNL SLPSTQSLNI KSEPVSPPRD
410 420 430 440 450
RTTTPSRYPQ HTRHEAGRSP VDSLSSCSSS YDGSDREDHR NEFHSPIGLT
460 470
RPSPDERESP SVKRMRLSEG WAT
Length:473
Mass (Da):51,217
Last modified:November 26, 2014 - v1
Checksum:i3D7C3B3F641C2C1F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR07007384 Genomic DNA No translation available.
RefSeqiXP_006224017.1, XM_006223955.3
XP_006224019.1, XM_006223957.3
XP_006231793.1, XM_006231731.2
XP_006231795.1, XM_006231733.3
XP_008758864.1, XM_008760642.2
XP_008773249.1, XM_008775027.2
XP_017446652.1, XM_017591163.1
XP_017449843.1, XM_017594354.1

Genome annotation databases

EnsembliENSRNOT00000076710; ENSRNOP00000068307; ENSRNOG00000033134
GeneIDi499497
KEGGirno:499497

Similar proteinsi

Entry informationi

Entry nameiMEF2C_RAT
AccessioniPrimary (citable) accession number: A0A096MJY4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 25, 2017
Last sequence update: November 26, 2014
Last modified: April 25, 2018
This is version 32 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health