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Protein

Myocyte-specific enhancer factor 2D

Gene

Mef2d

Organism
Mus musculus (Mouse)
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.2 Publications

Regions

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

GO - Molecular functioni

  • activating transcription factor binding Source: MGI
  • DNA binding Source: MGI
  • DNA binding transcription factor activity Source: MGI
  • enzyme binding Source: BHF-UCL
  • histone deacetylase binding Source: MGI
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • RNA polymerase II proximal promoter sequence-specific DNA binding Source: NTNU_SB
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: MGI
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: MGI
  • transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: NTNU_SB

GO - Biological processi

  • adult heart development Source: Ensembl
  • apoptotic process Source: UniProtKB-KW
  • chondrocyte differentiation Source: MGI
  • endochondral ossification Source: MGI
  • nervous system development Source: UniProtKB-KW
  • osteoblast differentiation Source: MGI
  • positive regulation of transcription, DNA-templated Source: MGI
  • positive regulation of transcription by RNA polymerase II Source: NTNU_SB
  • positive regulation of vascular smooth muscle cell proliferation Source: MGI
  • regulation of transcription, DNA-templated Source: MGI
  • skeletal muscle cell differentiation Source: MGI

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-MMU-375170 CDO in myogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Myocyte-specific enhancer factor 2D
Gene namesi
Name:Mef2d
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:99533 Mef2d

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
Mutagenesisi20T → A: No change in DNA-binding activity. 1 Publication1
Mutagenesisi20T → D: Dramatic decrease in DNA-binding. 1 Publication1
Mutagenesisi121S → A: Abolishes phosphorylation by PKA. No change in protein levels. Loss of protein stability on PKA stimulation. Loss of PKA-mediated repression. No change in interaction with HDAC4 in response to PKA; when associated with A-190. 1 Publication1
Mutagenesisi190S → A: Abolishes phosphorylation by PKA. No change in protein levels. Loss of protein stability on PKA stimulation mediated repression. No change in interaction with HDAC4 in response to PKA; when associated with A-121. 1 Publication1
Mutagenesisi437S → A: Loss of calpain/Cdk5-mediated neuron apoptosis. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001994361 – 514Myocyte-specific enhancer factor 2DAdd BLAST514

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei98PhosphoserineCombined sources1
Modified residuei106PhosphoserineCombined sources1
Modified residuei110PhosphoserineCombined sources1
Modified residuei121Phosphoserine; by PKA1 Publication1
Modified residuei180Phosphoserine; by MAPK7By similarity1
Modified residuei190Phosphoserine; by PKA1 Publication1
Modified residuei231PhosphoserineCombined sources1
Modified residuei245N6-acetyllysineBy similarity1
Modified residuei251PhosphoserineCombined sources1
Modified residuei432N6-acetyllysine; alternateBy similarity1
Cross-linki432Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Modified residuei437Phosphoserine1 Publication1
Isoform Muscle (identifier: Q63943-2)
Modified residuei97PhosphoserineCombined sources1
Modified residuei107PhosphothreonineCombined sources1

Post-translational modificationi

Phosphorylated on Ser-437 is which is required for Lys-432 sumoylation and inhibits transcriptional activity. Phosphorylation on this residue by CDK5 is dependent on p35 and calpains. Phosphorylated by PKA at Ser-121 and Ser-190 represses transcriptional activity in embryonic and postnatal skeletal muscle, and stabilizes protein levels. No in vitro phosphorylation by PKA on Thr-20. Phosphorylated and activated by CaMK4 (By similarity).By similarity
Acetylated on Lys-432 by CREBBP. Acetylated by EP300. Deacetylated by SIRT1 and HDAC3 (By similarity).By similarity
Sumoylated on Lys-432 with SUMO2 but not SUMO1; which inhibits transcriptional activity and myogenic activity. Desumoylated by SENP3 (By similarity).By similarity
Proteolytically cleaved in cerebellar granule neurons by caspase 7 following neurotoxicity. Preferentially cleaves the CDK5-mediated hyperphosphorylated form which leads to neuron apoptosis and transcriptional inactivation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei288 – 289CleavageCurated2

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ63943
PaxDbiQ63943
PRIDEiQ63943

PTM databases

iPTMnetiQ63943
PhosphoSitePlusiQ63943

Miscellaneous databases

PMAP-CutDBiQ63943

Expressioni

Tissue specificityi

Widely expressed though mainly restricted to skeletal and cardiac muscle, brain, neurons and lymphocytes. Differentially expressed depending on if isoforms contain the beta domain or not, with the total expression of the beta domain-lacking isoforms vastly exceding that of the beta domain-containing isoforms. Isoforms containing the beta domain are expressed primarily in skeletal and cardiac muscle and in brain. Also present in lung and testis. Splicing to include the beta domain is induced in differentiating myocytes. Isoforms lacking the beta domain are expressed less abundantly in skeletal muscle, brain and lymphocytes, and are uniquely found in ovary, liver, spleen and kidney. In embryos, the beta domain-containing and beta domain-lacking isoforms are equally expressed. Also expressed cerebellar granule neurons and other regions of the CNS. Highest levels in the olfactory bulb, cortex, hippocampus, thalamus and cerebellum.3 Publications

Developmental stagei

In the developing cerebellum, increasing levels after birth. The majority of this increase occurs around postnataL day 9 reaching a peak at postnatal day 15-18 which is maintained in adults.1 Publication

Gene expression databases

BgeeiENSMUSG00000001419
CleanExiMM_MEF2D
ExpressionAtlasiQ63943 baseline and differential
GenevisibleiQ63943 MM

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

GO - Molecular functioni

  • activating transcription factor binding Source: MGI
  • enzyme binding Source: BHF-UCL
  • histone deacetylase binding Source: MGI
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi201384, 4 interactors
ELMiQ63943
IntActiQ63943, 5 interactors
MINTiQ63943
STRINGi10090.ENSMUSP00000001455

Structurei

3D structure databases

ProteinModelPortaliQ63943
SMRiQ63943
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 domainBy similarity7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi3 – 31Arg/Lys-rich (basic)Add BLAST29
Compositional biasi252 – 255Poly-Pro4
Compositional biasi365 – 402Gln/Pro-richAdd BLAST38
Compositional biasi444 – 449Poly-Pro6

Sequence similaritiesi

Belongs to the MEF2 family.Curated

Phylogenomic databases

eggNOGiKOG0014 Eukaryota
COG5068 LUCA
GeneTreeiENSGT00390000011828
HOGENOMiHOG000230620
HOVERGENiHBG053944
InParanoidiQ63943
KOiK09262
OMAiGNISAWQ
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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Non-muscle (identifier: Q63943-1) [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 YGSSVPAPNF AMPVTVPVSN
160 170 180 190 200
QSSMQFSNPS SSLVTPSLVT SSLTDPRLLS PQQPALQRNS VSPGLPQRPA
210 220 230 240 250
SAGAMLGGDL NSANGACPSP VGNGYVSARA SPGLLPVANG NSLNKVIPAK
260 270 280 290 300
SPPPPTHNTQ LGAPSRKPDL RVITSQGGKG LMHHLTEDHL DLNNAQRLGV
310 320 330 340 350
SQSTHSLTTP VVSVATPSLL SQGLPFSSMP TAYNTDYQLP SAELSSLPAF
360 370 380 390 400
SSPAGLALGN VTAWQQPQPP QQPQPPQPPQ SQPQPPQPQP QQPPQQQPHL
410 420 430 440 450
VPVSLSNLIP GSPLPHVGAA LTVTTHPHIS IKSEPVSPSR ERSPAPPPPA
460 470 480 490 500
VFPAARPEPG EGLSSPAGGS YETGDRDDGR GDFGPTLGLL RPAPEPEAEG
510
SAVKRMRLDT WTLK
Length:514
Mass (Da):55,065
Last modified:July 27, 2011 - v2
Checksum:i34833264CE22C63F
GO
Isoform Muscle (identifier: Q63943-2) [UniParc]FASTAAdd to basket

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

Show »
Length:514
Mass (Da):55,350
Checksum:iB823D233F0492DE0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti287E → G in AAB29973 (PubMed:8114702).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00625387 – 132TLRKK…FRRYG → ALHNNDRECESPEVDEAFAL TPQTEEKYKKIDEEKYKKID EEFDKMMQSYRLA in isoform Muscle. 1 PublicationAdd BLAST46
Alternative sequenceiVSP_006254286 – 292Missing in isoform Muscle. 1 Publication7

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S68893 mRNA Translation: AAB29973.1
S68895 mRNA Translation: AAB29974.1
AC137525 Genomic DNA No translation available.
CCDSiCCDS79939.1 [Q63943-1]
PIRiB56201
RefSeqiNP_001297516.1, NM_001310587.1 [Q63943-1]
XP_006501152.1, XM_006501089.2 [Q63943-1]
XP_017174961.1, XM_017319472.1 [Q63943-1]
UniGeneiMm.28184
Mm.485397

Genome annotation databases

EnsembliENSMUST00000107559; ENSMUSP00000103184; ENSMUSG00000001419 [Q63943-1]
GeneIDi17261
KEGGimmu:17261
UCSCiuc008pua.1 mouse [Q63943-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiMEF2D_MOUSE
AccessioniPrimary (citable) accession number: Q63943
Secondary accession number(s): E9QKS9, Q63944
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 27, 2011
Last modified: May 23, 2018
This is version 147 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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