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UniProtKB - Q06413 (MEF2C_HUMAN)

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Protein

Myocyte-specific enhancer factor 2C

Gene

MEF2C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. 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). Isoform 3 and isoform 4, which lack the repressor domain, are more active than isoform 1 and isoform 2.By similarity6 Publications

Regions

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

GO - Molecular functioni

Complete GO annotation...

GO - Biological processi

Complete GO annotation...

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-198753. ERK/MAPK targets.
R-HSA-2151201. Transcriptional activation of mitochondrial biogenesis.
R-HSA-375170. CDO in myogenesis.
R-HSA-400253. Circadian Clock.
SignaLinkiQ06413.
SIGNORiQ06413.

Names & Taxonomyi

Protein namesi
Recommended name:
Myocyte-specific enhancer factor 2C
Gene namesi
Name:MEF2C
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:6996. MEF2C.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Alzheimers_University_of_Toronto
  • intracellular membrane-bounded organelle Source: HPA
  • nuclear speck Source: BHF-UCL
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • postsynapse Source: GOC
  • protein complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Mental retardation, autosomal dominant 20 (MRD20)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by severe mental retardation, absent speech, hypotonia, poor eye contact and stereotypic movements. Dysmorphic features include high broad forehead with variable small chin, short nose with anteverted nares, large open mouth, upslanted palpebral fissures and prominent eyebrows. Some patients have seizures.
See also OMIM:613443

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi116K → R: Reduced acetylation. Further reduction in acetylation; when associated with R-119. Complete loss of acetylation, 15% less transactivation activity and slightly reduced DNA binding; when associated with R-119; R-234; R-239; R-252 and R-262. 1 Publication1
Mutagenesisi119K → R: Reduced acetylation. Further reduction in acetylation; when associated with R-119. Complete loss of acetylation, 15% less transactivation activity and slightly reduced DNA binding; when associated with R-116; R-234; R-239; R-252 and R-262. 1 Publication1
Mutagenesisi234K → R: Reduced acetylation. Complete loss of acetylation, 15% less transactivation activity and slightly reduced DNA binding; when associated with R-116; R-119; R-239; R-252 and R-264. 1 Publication1
Mutagenesisi239K → R: Reduced acetylation. Complete loss of acetylation, 15% less transactivation activity and slightly reduced DNA binding; when associated with R-116; R-119; R-234; R-252 and R-264. 1 Publication1
Mutagenesisi252K → R: Reduced acetylation. Complete loss of acetylation, 15% less transactivation activity and slightly reduced DNA binding; when associated with R-116; R-119; R-234; R-239 and R-264. 1 Publication1
Mutagenesisi264K → R: Reduced acetylation. Complete loss of acetylation, 15% less transactivation activity and slightly reduced DNA binding; when associated with R-116; R-119; R-234; R-239 and R-252. 1 Publication1
Mutagenesisi271S → A: No effect on transcriptional activation. 1 Publication1
Mutagenesisi272E → Q: Reduced transcriptional activation. Completely abolishes transcriptional activation; when associated with N-273 and N-275. 1 Publication1
Mutagenesisi273D → N: Reduced transcriptional activation. Completely abolishes transcriptional activation; when associated with Q-272 and N-275. 1 Publication1
Mutagenesisi275D → N: Reduced transcriptional activation. Completely abolishes transcriptional activation; when associated with Q-272 and N-273. 1 Publication1
Mutagenesisi293T → A: Abolishes MAPK14-mediated phosphorylation. No effect on MAPK7-mediated phosphorylation; when associated with A-300. 2 Publications1
Mutagenesisi300T → A: Abolishes MAPK14-mediated phosphorylation. No effect on MAPK7-mediated phosphorylation; when associated with A-293. 2 Publications1
Mutagenesisi387S → A: No change in transactivational activation for isoforms with or without the beta domain. 1 Publication1
Mutagenesisi391K → R: Abolishes sumoylation. 1 Publication1
Mutagenesisi396S → A or C: Abolishes sumoylation. Enhanced transcriptional activity. 3 Publications1
Mutagenesisi396S → A: No change in transactivational activation for isoforms with or without the beta domain. 3 Publications1
Mutagenesisi396S → E: No effect on sumoylation. No effect on transcriptional activity. 3 Publications1
Mutagenesisi419S → A: No effect on MAPK14-mediated phosphorylation. Abolishes MAPK7-mediated phosphorylation and reduces transactivation activity. 2 Publications1
Mutagenesisi432D → A: Abolishes cleavage by caspase 7. 1 Publication1

Keywords - Diseasei

Disease mutation, Epilepsy, Mental retardation

Organism-specific databases

DisGeNETi4208.
MalaCardsiMEF2C.
MIMi613443. phenotype.
OpenTargetsiENSG00000081189.
Orphaneti228384. 5q14.3 microdeletion syndrome.
PharmGKBiPA30734.

Polymorphism and mutation databases

BioMutaiMEF2C.
DMDMi2500875.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001994331 – 473Myocyte-specific enhancer factor 2CAdd BLAST473

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei4N6-acetyllysineBy similarity1
Modified residuei59Phosphoserine; by CK2By similarity1
Modified residuei98PhosphoserineBy similarity1
Modified residuei106PhosphoserineBy similarity1
Modified residuei110PhosphoserineBy similarity1
Modified residuei116N6-acetyllysine1 Publication1
Modified residuei119N6-acetyllysine1 Publication1
Modified residuei222PhosphoserineCombined sources1
Modified residuei228PhosphoserineCombined sources1
Modified residuei234N6-acetyllysine1 Publication1
Modified residuei239N6-acetyllysine1 Publication1
Modified residuei240PhosphoserineCombined sources1
Modified residuei252N6-acetyllysine1 Publication1
Modified residuei264N6-acetyllysine1 Publication1
Modified residuei293Phosphothreonine; by MAPK142 Publications1
Modified residuei300Phosphothreonine; by MAPK142 Publications1
Cross-linki391Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)2 Publications
Modified residuei396Phosphoserine; by CDK51 Publication1
Modified residuei419Phosphoserine; by MAPK72 Publications1
Modified residuei445PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation on Ser-59 enhances DNA binding activity (By similarity). Phosphorylation on Ser-396 is required for Lys-391 sumoylation and inhibits transcriptional activity.By similarity7 Publications
Acetylated by p300 on several sites in diffentiating myocytes. Acetylation on Lys-4 increases DNA binding and transactivation (By similarity).By similarity
Sumoylated on Lys-391 with SUMO2 but not by SUMO1 represses transcriptional activity.3 Publications
Proteolytically cleaved in cerebellar granule neurons, probably by caspase 7, following neurotoxicity. Preferentially cleaves the CDK5-mediated hyperphosphorylated form which leads to neuron apoptosis and transcriptional inactivation.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei432 – 433CleavageCurated2

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ06413.
PeptideAtlasiQ06413.
PRIDEiQ06413.

PTM databases

iPTMnetiQ06413.
PhosphoSitePlusiQ06413.

Expressioni

Tissue specificityi

Expressed in brain and skeletal muscle.1 Publication

Developmental stagei

Expression is highest during the early stages of postnatal development, at later stages levels greatly decrease.

Gene expression databases

BgeeiENSG00000081189.
CleanExiHS_MEF2C.
ExpressionAtlasiQ06413. baseline and differential.
GenevisibleiQ06413. HS.

Organism-specific databases

HPAiCAB068196.
CAB068197.
HPA005533.

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 (By similarity). Interacts with HDAC7 and CARM1 (By similarity). Interacts with HDAC4 and HDAC9; the interaction with HDACs represses transcriptional activity (PubMed:10523670, PubMed:11535832). Interacts with LPIN1. Interacts with MYOCD. Interacts with AKAP13 (By similarity). Interacts with FOXK1; the interaction inhibits MEF2C transactivation activity (By similarity).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MYLK2Q9H1R32EBI-2684075,EBI-356910

GO - Molecular functioni

  • activating transcription factor binding Source: UniProtKB
  • histone deacetylase binding Source: Ensembl
  • HMG box domain binding Source: Ensembl
  • protein heterodimerization activity Source: UniProtKB
Complete GO annotation...

Protein-protein interaction databases

BioGridi110372. 27 interactors.
DIPiDIP-40857N.
IntActiQ06413. 18 interactors.
MINTiMINT-125556.

Structurei

3D structure databases

ProteinModelPortaliQ06413.
SMRiQ06413.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

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

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni271 – 278Beta domain8
Regioni368 – 399Transcription repressorAdd BLAST32

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi4 – 31Lys-rich (basic)Add BLAST28
Compositional biasi146 – 183Ser-richAdd BLAST38

Domaini

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

Sequence similaritiesi

Belongs to the MEF2 family.Curated

Phylogenomic databases

GeneTreeiENSGT00390000011828.
HOGENOMiHOG000230620.
HOVERGENiHBG053944.
InParanoidiQ06413.
KOiK04454.
OMAiHLVMPNS.
OrthoDBiEOG091G05BY.
PhylomeDBiQ06413.
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.
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

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q06413-1) [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
MGRKKIQITR IMDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNS 
        60         70         80         90        100
TNKLFQYAST DMDKVLLKYT EYNEPHESRT NSDIVETLRK KGLNGCDSPD 
       110        120        130        140        150
PDADDSVGHS PESEDKYRKI NEDIDLMISR QRLCAVPPPN FEMPVSIPVS 
       160        170        180        190        200
SHNSLVYSNP VSSLGNPNLL PLAHPSLQRN SMSPGVTHRP PSAGNTGGLM 
       210        220        230        240        250
GGDLTSGAGT SAGNGYGNPR NSPGLLVSPG NLNKNMQAKS 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):51,221
Last modified:November 1, 1997 - v1
Checksum:iA7982020BB8C8949
GO
Isoform 2 (identifier: Q06413-2) [UniParc]FASTAAdd to basket
Also known as: Muscle

The sequence of this isoform differs from the canonical sequence as follows:
     271-278: Missing.

Show »
Length:465
Mass (Da):50,336
Checksum:iA2059C6AACB2F07B
GO
Isoform 3 (identifier: Q06413-3) [UniParc]FASTAAdd to basket
Also known as: hMEF2C-delta32, Brain

The sequence of this isoform differs from the canonical sequence as follows:
     368-399: Missing.

Show »
Length:441
Mass (Da):47,872
Checksum:iBF94FD79A54FEEB1
GO
Isoform 4 (identifier: Q06413-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     87-134: Missing.
     271-278: Missing.

Show »
Length:417
Mass (Da):44,935
Checksum:i35B8B495FAB6FA3C
GO
Isoform 5 (identifier: Q06413-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     107-134: VGHSPESEDKYRKINEDIDLMISRQRLC → ALNKKENKGCESPDPDSSYALTPRTEEKYKKINEEFDNMIKSHKIP
     271-278: Missing.

Note: No experimental confirmation available.
Show »
Length:483
Mass (Da):52,328
Checksum:i54ECDC4D04211C48
GO
Isoform 6 (identifier: Q06413-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     87-134: TLRKKGLNGC...DLMISRQRLC → ALNKKENKGC...DNMIKSHKIP
     271-278: Missing.

Note: No experimental confirmation available.
Show »
Length:463
Mass (Da):50,242
Checksum:iB78282622DC98CE5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti390I → T in AL833268 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07822836S → R Probable disease-associated mutation found in a patient with infantile onset epileptic encephalopathy and autism spectrum disorder. 1 Publication1
Natural variantiVAR_07862139C → R Probable disease-associated mutation found in a patient with infantile onset epileptic encephalopathy and autism spectrum disorder. 1 PublicationCorresponds to variant dbSNP:rs796052729Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04333987 – 134Missing in isoform 4. 1 PublicationAdd BLAST48
Alternative sequenceiVSP_04625187 – 134TLRKK…RQRLC → ALNKKENKGCESPDPDSSYA LTPRTEEKYKKINEEFDNMI KSHKIP in isoform 6. 1 PublicationAdd BLAST48
Alternative sequenceiVSP_045478107 – 134VGHSP…RQRLC → ALNKKENKGCESPDPDSSYA LTPRTEEKYKKINEEFDNMI KSHKIP in isoform 5. 1 PublicationAdd BLAST28
Alternative sequenceiVSP_006248271 – 278Missing in isoform 2, isoform 4, isoform 5 and isoform 6. 4 Publications8
Alternative sequenceiVSP_006249368 – 399Missing in isoform 3. 1 PublicationAdd BLAST32

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L08895 mRNA. Translation: AAA59578.1.
S57212 mRNA. Translation: AAB25838.1.
FM163484 mRNA. Translation: CAQ57795.2.
AL833268 mRNA. No translation available.
AL833274 mRNA. No translation available.
AC008525 Genomic DNA. No translation available.
AC008835 Genomic DNA. No translation available.
CCDSiCCDS47244.1. [Q06413-6]
CCDS47245.1. [Q06413-1]
CCDS54877.1. [Q06413-4]
CCDS54878.1. [Q06413-5]
CCDS78034.1. [Q06413-2]
PIRiA47284.
RefSeqiNP_001124477.1. NM_001131005.2. [Q06413-6]
NP_001180276.1. NM_001193347.1. [Q06413-5]
NP_001180277.1. NM_001193348.1. [Q06413-4]
NP_001180278.1. NM_001193349.1.
NP_001180279.1. NM_001193350.1. [Q06413-1]
NP_001294931.1. NM_001308002.1. [Q06413-2]
NP_002388.2. NM_002397.4. [Q06413-1]
XP_005248568.1. XM_005248511.2. [Q06413-1]
XP_006714682.1. XM_006714619.2. [Q06413-1]
XP_006714688.1. XM_006714625.3. [Q06413-5]
XP_011541698.1. XM_011543396.2. [Q06413-1]
XP_011541702.1. XM_011543400.1. [Q06413-3]
XP_016864965.1. XM_017009476.1. [Q06413-2]
XP_016864966.1. XM_017009477.1. [Q06413-2]
XP_016864967.1. XM_017009478.1. [Q06413-6]
XP_016864968.1. XM_017009479.1. [Q06413-3]
XP_016864969.1. XM_017009480.1. [Q06413-3]
XP_016864970.1. XM_017009481.1. [Q06413-3]
UniGeneiHs.649965.

Genome annotation databases

EnsembliENST00000340208; ENSP00000340874; ENSG00000081189. [Q06413-5]
ENST00000424173; ENSP00000389610; ENSG00000081189. [Q06413-6]
ENST00000437473; ENSP00000396219; ENSG00000081189. [Q06413-1]
ENST00000504921; ENSP00000421925; ENSG00000081189. [Q06413-1]
ENST00000508569; ENSP00000423597; ENSG00000081189. [Q06413-2]
ENST00000514015; ENSP00000424606; ENSG00000081189. [Q06413-3]
ENST00000514028; ENSP00000426665; ENSG00000081189. [Q06413-3]
ENST00000625674; ENSP00000487430; ENSG00000081189. [Q06413-6]
ENST00000628656; ENSP00000487311; ENSG00000081189. [Q06413-4]
ENST00000629612; ENSP00000486554; ENSG00000081189. [Q06413-2]
ENST00000636294; ENSP00000490473; ENSG00000081189. [Q06413-1]
ENST00000636998; ENSP00000490630; ENSG00000081189. [Q06413-3]
ENST00000637732; ENSP00000490241; ENSG00000081189. [Q06413-3]
GeneIDi4208.
KEGGihsa:4208.
UCSCiuc003kjj.4. human. [Q06413-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiMEF2C_HUMAN
AccessioniPrimary (citable) accession number: Q06413
Secondary accession number(s): C9JMZ0, D7F7N5, F8W7V7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: July 5, 2017
This is version 164 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 5
    Human chromosome 5: 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