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Protein

Myocyte-specific enhancer factor 2D

Gene

MEF2D

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT]4TAR-3', found in numerous muscle-specific, growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. Plays a critical role in the regulation of neuronal apoptosis (By similarity).By similarity5 Publications

Regions

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

GO - Molecular functioni

GO - Biological processi

  • adult heart development Source: UniProtKB
  • apoptotic process Source: UniProtKB-KW
  • chondrocyte differentiation Source: Ensembl
  • endochondral ossification Source: Ensembl
  • muscle organ development Source: ProtInc
  • nervous system development Source: UniProtKB-KW
  • osteoblast differentiation Source: Ensembl
  • positive regulation of transcription by RNA polymerase II Source: UniProtKB
  • positive regulation of vascular smooth muscle cell proliferation Source: BHF-UCL
  • skeletal muscle cell differentiation Source: Ensembl

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-2151201 Transcriptional activation of mitochondrial biogenesis
R-HSA-375170 CDO in myogenesis
R-HSA-400253 Circadian Clock
SignaLinkiQ14814
SIGNORiQ14814

Names & Taxonomyi

Protein namesi
Recommended name:
Myocyte-specific enhancer factor 2D
Gene namesi
Name:MEF2D
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000116604.17
HGNCiHGNC:6997 MEF2D
MIMi600663 gene
neXtProtiNX_Q14814

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

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi180S → A: Abolishes MAPK7- and EGF-mediated transcriptional activation. 1 Publication1
Mutagenesisi286T → A: Same transcriptional activity as for isoforms with beta domain. 1 Publication1
Mutagenesisi287E → Q: Abolishes transcriptional activity; when associated with N-288 and N-291. 1 Publication1
Mutagenesisi288D → A: Abolishes cleavage by caspase 7. 2 Publications1
Mutagenesisi288D → N: Abolishes transcriptional activity; when associated with Q-287 and N-291. 2 Publications1
Mutagenesisi289H → A: Same transcriptional activity as for isoforms with beta domain. 1 Publication1
Mutagenesisi291D → N: Abolishes transcriptional activity; when associated with Q-287 and N-288. 1 Publication1
Mutagenesisi437S → A: No effect on MAPK7- or EGF-mediated transcriptional activity. 1 Publication1
Mutagenesisi438I → A: Abolishes K-439 sumoylation. 1 Publication1
Mutagenesisi439K → R: Abolishes sumoylation and acetylation. 2 Publications1
Mutagenesisi444S → A: Abolishes K-439 sumoylation. Reduced neurotoxin-induced apoptosis of neuronal cells. More resistant to degradation. 3 Publications1
Mutagenesisi444S → E: No effect on K-439 sumoylation. 3 Publications1

Organism-specific databases

DisGeNETi4209
OpenTargetsiENSG00000116604
PharmGKBiPA30735

Polymorphism and mutation databases

DMDMi2500876

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001994351 – 521Myocyte-specific enhancer factor 2DAdd BLAST521

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei98PhosphoserineBy similarity1
Modified residuei106PhosphoserineBy similarity1
Modified residuei110PhosphoserineBy similarity1
Modified residuei121Phosphoserine; by PKACombined sources1 Publication1
Modified residuei180Phosphoserine; by MAPK7Combined sources1 Publication1
Modified residuei190Phosphoserine; by PKABy similarity1
Modified residuei231PhosphoserineCombined sources1
Modified residuei245N6-acetyllysineCombined sources1
Modified residuei251PhosphoserineCombined sources1
Modified residuei439N6-acetyllysine; alternate1 Publication1
Cross-linki439Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Modified residuei444Phosphoserine3 Publications1

Post-translational modificationi

Phosphorylated on Ser-444 by CDK5 is required for Lys-439 sumoylation and inhibits transcriptional activity. In neurons, enhanced CDK5 activity induced by neurotoxins promotes caspase 3-mediated cleavage leading to neuron apoptosis. Phosphorylation on Ser-180 can be enhanced by EGF. Phosphorylated and activated by CaMK4.8 Publications
Acetylated on Lys-439 by CREBBP. Acetylated by EP300. Deacetylated by SIRT1 and HDAC3.3 Publications
Sumoylated on Lys-439 with SUMO2 but not SUMO1; which inhibits transcriptional activity and myogenic activity. Desumoylated by SENP3.3 Publications
Proteolytically cleaved in cerebellar granule neurons on several sites by caspase 7 following neurotoxicity. Preferentially cleaves the CDK5-mediated hyperphosphorylated form which leads to neuron apoptosis and transcriptional inactivation (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei288 – 289CleavageCurated2

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ14814
MaxQBiQ14814
PaxDbiQ14814
PeptideAtlasiQ14814
PRIDEiQ14814
ProteomicsDBi60190
60191 [Q14814-2]
60192 [Q14814-3]
60193 [Q14814-4]
60194 [Q14814-5]
60195 [Q14814-6]

PTM databases

iPTMnetiQ14814
PhosphoSitePlusiQ14814

Miscellaneous databases

PMAP-CutDBiQ14814

Expressioni

Developmental stagei

Present in myotubes and also in undifferentiated myoblasts.

Gene expression databases

BgeeiENSG00000116604
CleanExiHS_MEF2D
ExpressionAtlasiQ14814 baseline and differential
GenevisibleiQ14814 HS

Organism-specific databases

HPAiHPA004807
HPA007114

Interactioni

Subunit structurei

Interacts with MYOG (By similarity). 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 HDAC4 (in undifferentiating cells); the interaction translocates MEF2D to nuclear dots. Forms a heterodimer with MEF2A. Interacts with MAPK7; the interaction phosphorylates but does not activate MEF2D (By similarity). Interacts with CCAR2 and HDAC3.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
YwhaqP682553EBI-2829828,EBI-400680From Rattus norvegicus.

GO - Molecular functioni

  • activating transcription factor binding Source: UniProtKB
  • histone deacetylase binding Source: UniProtKB
  • protein heterodimerization activity Source: Ensembl
  • protein homodimerization activity Source: Ensembl

Protein-protein interaction databases

BioGridi110373, 38 interactors
ELMiQ14814
IntActiQ14814, 13 interactors
MINTiQ14814
STRINGi9606.ENSP00000271555

Chemistry databases

BindingDBiQ14814

Structurei

3D structure databases

ProteinModelPortaliQ14814
SMRiQ14814
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini3 – 57MADS-boxPROSITE-ProRule annotationAdd BLAST55

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni286 – 292Beta domain7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi3 – 31Arg/Lys-rich (basic)Add BLAST29
Compositional biasi252 – 255Poly-Pro4
Compositional biasi365 – 404Gln/Pro-richAdd BLAST40
Compositional biasi451 – 456Poly-Pro6

Domaini

The beta domain, missing in a number of isoforms, is required for enhancement of transcriptional activity.

Sequence similaritiesi

Belongs to the MEF2 family.Curated

Phylogenomic databases

eggNOGiKOG0014 Eukaryota
COG5068 LUCA
GeneTreeiENSGT00390000011828
HOVERGENiHBG053944
InParanoidiQ14814
KOiK09262
OMAiGNISAWQ
OrthoDBiEOG091G05BY
PhylomeDBiQ14814
TreeFamiTF314067

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

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform MEF2DAB (identifier: Q14814-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGRKKIQIQR ITDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNH
60 70 80 90 100
SNKLFQYAST DMDKVLLKYT EYNEPHESRT NADIIETLRK KGFNGCDSPE
110 120 130 140 150
PDGEDSLEQS PLLEDKYRRA SEELDGLFRR YGSTVPAPNF AMPVTVPVSN
160 170 180 190 200
QSSLQFSNPS GSLVTPSLVT SSLTDPRLLS PQQPALQRNS VSPGLPQRPA
210 220 230 240 250
SAGAMLGGDL NSANGACPSP VGNGYVSARA SPGLLPVANG NSLNKVIPAK
260 270 280 290 300
SPPPPTHSTQ LGAPSRKPDL RVITSQAGKG LMHHLTEDHL DLNNAQRLGV
310 320 330 340 350
SQSTHSLTTP VVSVATPSLL SQGLPFSSMP TAYNTDYQLT SAELSSLPAF
360 370 380 390 400
SSPGGLSLGN VTAWQQPQQP QQPQQPQPPQ QQPPQPQQPQ PQQPQQPQQP
410 420 430 440 450
PQQQSHLVPV SLSNLIPGSP LPHVGAALTV TTHPHISIKS EPVSPSRERS
460 470 480 490 500
PAPPPPAVFP AARPEPGDGL SSPAGGSYET GDRDDGRGDF GPTLGLLRPA
510 520
PEPEAEGSAV KRMRLDTWTL K
Length:521
Mass (Da):55,938
Last modified:November 1, 1997 - v1
Checksum:i5C9790AD598619BA
GO
Isoform MEF2DA'B (identifier: Q14814-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     87-132: TLRKKGFNGC...ELDGLFRRYG → ALHKKHRECE...DKMMQSYRLA

Show »
Length:520
Mass (Da):56,091
Checksum:i9B39CB2A3570EB74
GO
Isoform MEF2D0B (identifier: Q14814-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     87-132: Missing.

Show »
Length:475
Mass (Da):50,680
Checksum:iBCA6D1EF6885A467
GO
Isoform MEF2DA0 (identifier: Q14814-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     286-292: Missing.

Show »
Length:514
Mass (Da):55,114
Checksum:i425430A7A0F69549
GO
Isoform MEF2DA'0 (identifier: Q14814-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     87-132: TLRKKGFNGC...ELDGLFRRYG → ALHKKHRECE...DKMMQSYRLA
     286-292: Missing.

Show »
Length:513
Mass (Da):55,267
Checksum:i2CC3FD705A1C8D1F
GO
Isoform MEF2D00 (identifier: Q14814-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     87-132: Missing.
     286-292: Missing.

Show »
Length:468
Mass (Da):49,856
Checksum:iBFFEBF282D6519F7
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022155434P → S. Corresponds to variant dbSNP:rs2274315Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00625187 – 132Missing in isoform MEF2D0B and isoform MEF2D00. 1 PublicationAdd BLAST46
Alternative sequenceiVSP_00625087 – 132TLRKK…FRRYG → ALHKKHRECESPEVDEVFAL TPQTEEKYKKIDEEFDKMMQ SYRLA in isoform MEF2DA'B and isoform MEF2DA'0. 1 PublicationAdd BLAST46
Alternative sequenceiVSP_006252286 – 292Missing in isoform MEF2DA0, isoform MEF2DA'0 and isoform MEF2D00. 2 Publications7

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L16794 mRNA Translation: AAA93194.1
L16795 Genomic DNA Translation: AAA59579.1
AL139412 Genomic DNA No translation available.
CH471121 Genomic DNA Translation: EAW52948.1
CH471121 Genomic DNA Translation: EAW52952.1
BC040949 mRNA Translation: AAH40949.1
BC054520 mRNA Translation: AAH54520.1
CCDSiCCDS1143.1 [Q14814-1]
CCDS60304.1 [Q14814-4]
PIRiI53124
RefSeqiNP_001258558.1, NM_001271629.1 [Q14814-4]
NP_005911.1, NM_005920.3 [Q14814-1]
XP_005245226.1, XM_005245169.4 [Q14814-1]
XP_005245227.1, XM_005245170.3 [Q14814-1]
XP_006711393.1, XM_006711330.3 [Q14814-1]
XP_006711395.1, XM_006711332.3 [Q14814-2]
XP_006711396.1, XM_006711333.2 [Q14814-4]
XP_006711397.1, XM_006711334.3 [Q14814-5]
XP_011507871.1, XM_011509569.2 [Q14814-1]
XP_016856803.1, XM_017001314.1 [Q14814-4]
XP_016856804.1, XM_017001315.1 [Q14814-4]
UniGeneiHs.314327
Hs.744524

Genome annotation databases

EnsembliENST00000348159; ENSP00000271555; ENSG00000116604 [Q14814-1]
ENST00000360595; ENSP00000353803; ENSG00000116604 [Q14814-4]
ENST00000464356; ENSP00000476788; ENSG00000116604 [Q14814-5]
GeneIDi4209
KEGGihsa:4209
UCSCiuc001fpb.5 human [Q14814-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiMEF2D_HUMAN
AccessioniPrimary (citable) accession number: Q14814
Secondary accession number(s): D3DVC0
, Q14815, Q5T9U5, Q5T9U6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: July 18, 2018
This is version 177 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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