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Q06413 (MEF2C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Myocyte-specific enhancer factor 2C
Gene names
Name:MEF2C
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length473 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6 Ref.7 Ref.12 Ref.13 Ref.15 Ref.17

Subunit structure

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 By similarity. Interacts with HDAC4, HDAC7 AND HDAC9; the interaction WITH HDACs represses transcriptional activity. Interacts with MYOCD By similarity. Ref.9 Ref.11 Ref.17

Subcellular location

Nucleus.

Tissue specificity

Expressed in brain and skeletal muscle. Ref.8

Developmental stage

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

Domain

The beta domain, missing in a number of isoforms, is required for enhancement of transcriptional activity By similarity. Ref.15

Post-translational modification

Phosphorylation on Ser-59 enhances DNA binding activity By similarity. Phosphorylation on Ser-396 is required for Lys-391 sumoylation and inhibits transcriptional activity. Ref.14 Ref.16 Ref.18

Acetylated by p300 on several sites in diffentiating myocytes. Acetylation on Lys-4 increases DNA binding and transactivation By similarity. Ref.17

Sumoylated on Lys-391 with SUMO2 but not by SUMO1 represses transcriptional activity. Ref.14 Ref.16 Ref.18

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. Ref.6 Ref.7 Ref.10 Ref.13

Involvement in disease

Mental retardation, autosomal dominant 20 (MRD20) [MIM:613443]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19

Sequence similarities

Belongs to the MEF2 family.

Contains 1 MADS-box domain.

Contains 1 Mef2-type DNA-binding domain.

Ontologies

Keywords
   Biological processApoptosis
Differentiation
Neurogenesis
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DiseaseEpilepsy
Mental retardation
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

B cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

B cell receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

MAPK cascade

Inferred from direct assay PubMed 9858528. Source: UniProtKB

MyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

blood vessel development

Inferred from sequence or structural similarity. Source: UniProtKB

blood vessel remodeling

Inferred from sequence or structural similarity. Source: UniProtKB

cardiac muscle hypertrophy in response to stress

Inferred from electronic annotation. Source: Ensembl

cardiac ventricle formation

Inferred from sequence or structural similarity. Source: UniProtKB

cartilage morphogenesis

Inferred from electronic annotation. Source: Ensembl

cell morphogenesis involved in neuron differentiation

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

cellular response to calcium ion

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to drug

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to fluid shear stress

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to glucose stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to lipopolysaccharide

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to parathyroid hormone stimulus

Inferred from direct assay PubMed 17696759. Source: UniProtKB

cellular response to retinoic acid

Inferred from electronic annotation. Source: Ensembl

cellular response to transforming growth factor beta stimulus

Inferred from direct assay PubMed 9770491. Source: UniProtKB

cellular response to trichostatin A

Inferred from sequence or structural similarity. Source: UniProtKB

chondrocyte differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

dentate gyrus development

Inferred from electronic annotation. Source: Ensembl

embryonic viscerocranium morphogenesis

Inferred from electronic annotation. Source: Ensembl

endochondral ossification

Inferred from sequence or structural similarity. Source: UniProtKB

epithelial cell proliferation involved in renal tubule morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

germinal center formation

Inferred from sequence or structural similarity. Source: UniProtKB

glomerulus morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

heart development

Inferred from expression pattern PubMed 10458488. Source: UniProtKB

heart looping

Inferred from sequence or structural similarity. Source: UniProtKB

humoral immune response

Inferred from sequence or structural similarity. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

learning or memory

Inferred from sequence or structural similarity. Source: UniProtKB

melanocyte differentiation

Inferred from sequence or structural similarity PubMed 21610032. Source: UniProtKB

monocyte differentiation

Inferred from electronic annotation. Source: Ensembl

muscle cell differentiation

Traceable author statement. Source: Reactome

muscle cell fate determination

Inferred from sequence or structural similarity. Source: UniProtKB

muscle organ development

Traceable author statement Ref.2. Source: ProtInc

myotube differentiation

Inferred from expression pattern Ref.2. Source: UniProtKB

negative regulation of epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of gene expression

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of neuron apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of ossification

Inferred from direct assay PubMed 17696759. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 18079734. Source: BHF-UCL

nephron tubule epithelial cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

nervous system development

Traceable author statement Ref.2. Source: ProtInc

neural crest cell differentiation

Inferred from sequence or structural similarity PubMed 21610032. Source: UniProtKB

neuron development

Inferred from sequence or structural similarity. Source: UniProtKB

neuron differentiation

Inferred from expression pattern Ref.2. Source: UniProtKB

neuron migration

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

osteoblast differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

outflow tract morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

palate development

Inferred from electronic annotation. Source: Ensembl

platelet formation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of B cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of MAP kinase activity

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

positive regulation of alkaline phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of behavioral fear response

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of bone mineralization

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cardiac muscle cell differentiation

Inferred from direct assay PubMed 9857019. Source: UniProtKB

positive regulation of cardiac muscle cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cardiac muscle hypertrophy

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation in bone marrow

Inferred from electronic annotation. Source: Ensembl

positive regulation of gene expression

Inferred from direct assay PubMed 21556048PubMed 9857019. Source: UniProtKB

positive regulation of macrophage apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of muscle cell differentiation

Traceable author statement. Source: Reactome

positive regulation of myoblast differentiation

Inferred from mutant phenotype PubMed 9770491. Source: UniProtKB

positive regulation of neuron differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of osteoblast differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein homodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of skeletal muscle cell differentiation

Inferred from direct assay PubMed 21556048. Source: UniProtKB

positive regulation of skeletal muscle tissue development

Inferred from mutant phenotype PubMed 9770491. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 15486975Ref.2. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 17696759PubMed 11744164PubMed 11744164PubMed 11744164. Source: UniProtKB

primary heart field specification

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of N-methyl-D-aspartate selective glutamate receptor activity

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

regulation of dendritic spine development

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

regulation of excitatory postsynaptic membrane potential

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

regulation of germinal center formation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of megakaryocyte differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of neuron apoptotic process

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

regulation of neurotransmitter secretion

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

regulation of sarcomere organization

Inferred from electronic annotation. Source: Ensembl

regulation of synapse assembly

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

regulation of synaptic activity

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of synaptic plasticity

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

regulation of synaptic transmission, glutamatergic

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 24008018. Source: Alzheimers_University_of_Toronto

renal tubule morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

response to ischemia

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

response to virus

Inferred from expression pattern PubMed 21170291. Source: UniProtKB

response to vitamin E

Inferred from electronic annotation. Source: Ensembl

secondary heart field specification

Inferred from sequence or structural similarity. Source: UniProtKB

sinoatrial valve morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

skeletal muscle tissue development

Inferred from sequence or structural similarity. Source: UniProtKB

smooth muscle cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

stress-activated MAPK cascade

Traceable author statement. Source: Reactome

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

ventricular cardiac muscle cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay Ref.2. Source: UniProtKB

cytosol

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

nuclear speck

Inferred from direct assay PubMed 18079734. Source: BHF-UCL

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 16510869PubMed 21170291Ref.2PubMed 9770491PubMed 11744164PubMed 11744164PubMed 11744164. Source: UniProtKB

protein complex

Inferred from direct assay PubMed 15486975. Source: UniProtKB

sarcomere

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionAT DNA binding

Inferred from direct assay PubMed 15486975. Source: UniProtKB

DNA binding

Inferred from direct assay PubMed 11744164PubMed 11744164. Source: UniProtKB

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from direct assay PubMed 15486975. Source: UniProtKB

RNA polymerase II core promoter sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.2. Source: UniProtKB

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

RNA polymerase II regulatory region sequence-specific DNA binding

Inferred from direct assay Ref.2. Source: UniProtKB

activating transcription factor binding

Inferred from physical interaction PubMed 11160896. Source: UniProtKB

chromatin binding

Inferred from electronic annotation. Source: Ensembl

core promoter proximal region sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

core promoter sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

miRNA binding

Inferred from direct assay PubMed 21170291. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 15486975PubMed 16510869PubMed 18588859PubMed 21556048. Source: UniProtKB

protein heterodimerization activity

Inferred from physical interaction PubMed 9858528. Source: UniProtKB

sequence-specific DNA binding RNA polymerase II transcription factor activity

Inferred from sequence or structural similarity PubMed 21610032. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 16043483. Source: BHF-UCL

transcription regulatory region DNA binding

Inferred from sequence or structural similarity. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MYLK2Q9H1R32EBI-2684075,EBI-356910

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q06413-1)

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.
Isoform 2 (identifier: Q06413-2)

Also known as: Muscle;

The sequence of this isoform differs from the canonical sequence as follows:
     271-278: Missing.
Isoform 3 (identifier: Q06413-3)

Also known as: hMEF2C-delta32; Brain;

The sequence of this isoform differs from the canonical sequence as follows:
     368-399: Missing.
Isoform 4 (identifier: Q06413-4)

The sequence of this isoform differs from the canonical sequence as follows:
     87-134: Missing.
     271-278: Missing.
Isoform 5 (identifier: Q06413-5)

The sequence of this isoform differs from the canonical sequence as follows:
     107-134: VGHSPESEDKYRKINEDIDLMISRQRLC → ALNKKENKGCESPDPDSSYALTPRTEEKYKKINEEFDNMIKSHKIP
     271-278: Missing.
Note: No experimental confirmation available.
Isoform 6 (identifier: Q06413-6)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 473473Myocyte-specific enhancer factor 2C
PRO_0000199433

Regions

Domain3 – 5755MADS-box
DNA binding58 – 8629Mef2-type Potential
Region271 – 2788Beta domain
Region368 – 39932Transcription repressor
Compositional bias4 – 3128Lys-rich (basic)
Compositional bias146 – 18338Ser-rich

Sites

Site432 – 4332Cleavage Probable

Amino acid modifications

Modified residue41N6-acetyllysine By similarity
Modified residue591Phosphoserine; by CK2 By similarity
Modified residue1161N6-acetyllysine Ref.17
Modified residue1191N6-acetyllysine Ref.17
Modified residue2341N6-acetyllysine Ref.17
Modified residue2391N6-acetyllysine Ref.17
Modified residue2521N6-acetyllysine Ref.17
Modified residue2641N6-acetyllysine Ref.17
Modified residue2931Phosphothreonine; by MAPK14 Ref.6 Ref.7
Modified residue3001Phosphothreonine; by MAPK14 Ref.6 Ref.7
Modified residue3961Phosphoserine; by CDK5 Ref.13
Modified residue4191Phosphoserine; by MAPK7 Ref.6 Ref.7
Cross-link391Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.16 Ref.18

Natural variations

Alternative sequence87 – 13448Missing in isoform 4.
VSP_043339
Alternative sequence87 – 13448TLRKK…RQRLC → ALNKKENKGCESPDPDSSYA LTPRTEEKYKKINEEFDNMI KSHKIP in isoform 6.
VSP_046251
Alternative sequence107 – 13428VGHSP…RQRLC → ALNKKENKGCESPDPDSSYA LTPRTEEKYKKINEEFDNMI KSHKIP in isoform 5.
VSP_045478
Alternative sequence271 – 2788Missing in isoform 2, isoform 4, isoform 5 and isoform 6.
VSP_006248
Alternative sequence368 – 39932Missing in isoform 3.
VSP_006249

Experimental info

Mutagenesis1161K → 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. Ref.17
Mutagenesis1191K → 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. Ref.17
Mutagenesis2341K → 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. Ref.17
Mutagenesis2391K → 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. Ref.17
Mutagenesis2521K → 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. Ref.17
Mutagenesis2641K → 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. Ref.17
Mutagenesis2711S → A: No effect on transcriptional activation. Ref.15
Mutagenesis2721E → Q: Reduced transcriptional activation. Completely abolishes transcriptional activation; when associated with N-273 and N-275. Ref.15
Mutagenesis2731D → N: Reduced transcriptional activation. Completely abolishes transcriptional activation; when associated with Q-272 and N-275. Ref.15
Mutagenesis2751D → N: Reduced transcriptional activation. Completely abolishes transcriptional activation; when associated with Q-272 and N-273. Ref.15
Mutagenesis2931T → A: Abolishes MAPK14-mediated phosphorylation. No effect on MAPK7-mediated phosphorylation; when associated with A-300. Ref.6 Ref.7
Mutagenesis3001T → A: Abolishes MAPK14-mediated phosphorylation. No effect on MAPK7-mediated phosphorylation; when associated with A-293. Ref.6 Ref.7
Mutagenesis3871S → A: No change in transactivational activation for isoforms with or without the beta domain. Ref.15
Mutagenesis3911K → R: Abolishes sumoylation. Ref.18
Mutagenesis3961S → A or C: Abolishes sumoylation. Enhanced transcriptional activity. Ref.13 Ref.15 Ref.18
Mutagenesis3961S → A: No change in transactivational activation for isoforms with or without the beta domain. Ref.13 Ref.15 Ref.18
Mutagenesis3961S → E: No effect on sumoylation. No effect on transcriptional activity. Ref.13 Ref.15 Ref.18
Mutagenesis4191S → A: No effect on MAPK14-mediated phosphorylation. Abolishes MAPK7-mediated phosphorylation and reduces transactivation activity. Ref.6 Ref.7
Mutagenesis4321D → A: Abolishes cleavage by caspase 7. Ref.12
Sequence conflict3901I → T in AL833268. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1997. Version 1.
Checksum: A7982020BB8C8949

FASTA47351,221
        10         20         30         40         50         60 
MGRKKIQITR IMDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNS TNKLFQYAST 

        70         80         90        100        110        120 
DMDKVLLKYT EYNEPHESRT NSDIVETLRK KGLNGCDSPD PDADDSVGHS PESEDKYRKI 

       130        140        150        160        170        180 
NEDIDLMISR QRLCAVPPPN FEMPVSIPVS SHNSLVYSNP VSSLGNPNLL PLAHPSLQRN 

       190        200        210        220        230        240 
SMSPGVTHRP PSAGNTGGLM GGDLTSGAGT SAGNGYGNPR NSPGLLVSPG NLNKNMQAKS 

       250        260        270        280        290        300 
PPPMNLGMNN RKPDLRVLIP PGSKNTMPSV SEDVDLLLNQ RINNSQSAQS LATPVVSVAT 

       310        320        330        340        350        360 
PTLPGQGMGG YPSAISTTYG TEYSLSSADL SSLSGFNTAS ALHLGSVTGW QQQHLHNMPP 

       370        380        390        400        410        420 
SALSQLGACT STHLSQSSNL SLPSTQSLNI KSEPVSPPRD RTTTPSRYPQ HTRHEAGRSP 

       430        440        450        460        470 
VDSLSSCSSS YDGSDREDHR NEFHSPIGLT RPSPDERESP SVKRMRLSEG WAT 

« Hide

Isoform 2 (Muscle) [UniParc].

Checksum: A2059C6AACB2F07B
Show »

FASTA46550,336
Isoform 3 (hMEF2C-delta32) (Brain) [UniParc].

Checksum: BF94FD79A54FEEB1
Show »

FASTA44147,872
Isoform 4 [UniParc].

Checksum: 35B8B495FAB6FA3C
Show »

FASTA41744,935
Isoform 5 [UniParc].

Checksum: 54ECDC4D04211C48
Show »

FASTA48352,328
Isoform 6 [UniParc].

Checksum: B78282622DC98CE5
Show »

FASTA46350,242

References

« Hide 'large scale' references
[1]"MEF2C, a MADS/MEF2-family transcription factor expressed in a laminar distribution in cerebral cortex."
Leifer D., Krainc D., Yu Y.-T., McDermott J., Breitbart R.E., Heng J., Neve R.L., Kosofsky B., Nadal-Ginard B., Lipton S.A.
Proc. Natl. Acad. Sci. U.S.A. 90:1546-1550(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
Tissue: Fetal brain and Muscle.
[2]"hMEF2C gene encodes skeletal muscle- and brain-specific transcription factors."
McDermott J.C., Cardoso M.C., Yu Y.-T., Andres V., Leifer D., Krainc D., Lipton S.A., Nadal-Ginard B.
Mol. Cell. Biol. 13:2564-2577(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Skeletal muscle.
[3]"Identification and characterization of a new splice variant of human MEF2C."
Infantino V., Convertini P., Palmieri F., Iacobazzi V.
Submitted (MAY-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
Tissue: Skeletal muscle.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 5 AND 6).
Tissue: Skeletal muscle.
[5]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C."
Kato Y., Kravchenko V.V., Tapping R.I., Han J., Ulevitch R.J., Lee J.-D.
EMBO J. 16:7054-7066(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-293; THR-300 AND SER-419, FUNCTION, MUTAGENESIS OF THR-293; THR-300 AND SER-419.
[7]"Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation."
Han J., Jiang Y., Li Z., Kravchenko V.V., Ulevitch R.J.
Nature 386:296-299(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-293; THR-300 AND SER-419, FUNCTION, MUTAGENESIS OF THR-293; THR-300 AND SER-419.
[8]"Characterization of myocyte enhancer factor 2 (MEF2) expression in B and T cells: MEF2C is a B cell-restricted transcription factor in lymphocytes."
Swanson B.J., Jaeck H.-M., Lyons G.E.
Mol. Immunol. 35:445-458(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[9]"HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor."
Wang A.H., Bertos N.R., Vezmar M., Pelletier N., Crosato M., Heng H.H., Th'ng J., Han J., Yang X.-J.
Mol. Cell. Biol. 19:7816-7827(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HDAC4.
[10]"Big mitogen-activated kinase regulates multiple members of the MEF2 protein family."
Kato Y., Zhao M., Morikawa A., Sugiyama T., Chakravortty D., Koide N., Yoshida T., Tapping R.I., Yang Y., Yokochi T., Lee J.D.
J. Biol. Chem. 275:18534-18540(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY MAPK7.
[11]"Cloning and characterization of a histone deacetylase, HDAC9."
Zhou X., Marks P.A., Rifkind R.A., Richon V.M.
Proc. Natl. Acad. Sci. U.S.A. 98:10572-10577(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HDAC9.
[12]"Dominant-interfering forms of MEF2 generated by caspase cleavage contribute to NMDA-induced neuronal apoptosis."
Okamoto S., Li Z., Ju C., Scholzke M.N., Mathews E., Cui J., Salvesen G.S., Bossy-Wetzel E., Lipton S.A.
Proc. Natl. Acad. Sci. U.S.A. 99:3974-3979(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING AT ASP-432, FUNCTION, MUTAGENESIS OF ASP-432.
[13]"Phosphorylation and alternative pre-mRNA splicing converge to regulate myocyte enhancer factor 2C activity."
Zhu B., Gulick T.
Mol. Cell. Biol. 24:8264-8275(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-396, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF SER-396, FUNCTION OF ISOFORMS.
[14]"Systematic identification and analysis of mammalian small ubiquitin-like modifier substrates."
Gocke C.B., Yu H., Kang J.
J. Biol. Chem. 280:5004-5012(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION.
[15]"Alternative pre-mRNA splicing governs expression of a conserved acidic transactivation domain in myocyte enhancer factor 2 factors of striated muscle and brain."
Zhu B., Ramachandran B., Gulick T.
J. Biol. Chem. 280:28749-28760(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF BETA DOMAIN, MUTAGENESIS OF SER-271; GLU-272; ASP-273; ASP-275; SER-387 AND SER-396.
[16]"Association with class IIa histone deacetylases upregulates the sumoylation of MEF2 transcription factors."
Gregoire S., Yang X.-J.
Mol. Cell. Biol. 25:2273-2287(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION AT LYS-391.
[17]"Myocyte enhancer factor 2 acetylation by p300 enhances its DNA binding activity, transcriptional activity, and myogenic differentiation."
Ma K., Chan J.K., Zhu G., Wu Z.
Mol. Cell. Biol. 25:3575-3582(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT LYS-116; LYS-119; LYS-234; LYS-239; LYS-252 AND LYS-264, INTERACTION WITH EP300, FUNCTION, DNA-BINDING, MUTAGENESIS OF LYS-116; LYS-119; LYS-234; LYS-239; LYS-252 AND LYS-264.
[18]"Phosphorylation-facilitated sumoylation of MEF2C negatively regulates its transcriptional activity."
Kang J., Gocke C.B., Yu H.
BMC Biochem. 7:5-5(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION AT LYS-391, MUTAGENESIS OF LYS-391 AND SER-396.
[19]"MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations."
Le Meur N., Holder-Espinasse M., Jaillard S., Goldenberg A., Joriot S., Amati-Bonneau P., Guichet A., Barth M., Charollais A., Journel H., Auvin S., Boucher C., Kerckaert J.P., David V., Manouvrier-Hanu S., Saugier-Veber P., Frebourg T., Dubourg C., Andrieux J., Bonneau D.
J. Med. Genet. 47:22-29(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN MRD20.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS47244.1. [Q06413-6]
CCDS47245.1. [Q06413-1]
CCDS54877.1. [Q06413-4]
CCDS54878.1. [Q06413-5]
PIRA47284.
RefSeqNP_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_002388.2. NM_002397.4. [Q06413-1]
XP_005248568.1. XM_005248511.1. [Q06413-1]
XP_006714681.1. XM_006714618.1. [Q06413-1]
XP_006714682.1. XM_006714619.1. [Q06413-1]
XP_006714684.1. XM_006714621.1. [Q06413-2]
XP_006714685.1. XM_006714622.1. [Q06413-6]
XP_006714686.1. XM_006714623.1. [Q06413-3]
XP_006714688.1. XM_006714625.1. [Q06413-5]
UniGeneHs.649965.

3D structure databases

ProteinModelPortalQ06413.
SMRQ06413. Positions 2-73.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110372. 26 interactions.
DIPDIP-40857N.
IntActQ06413. 16 interactions.
MINTMINT-125556.
STRING9606.ENSP00000396219.

PTM databases

PhosphoSiteQ06413.

Polymorphism databases

DMDM2500875.

Proteomic databases

MaxQBQ06413.
PaxDbQ06413.
PRIDEQ06413.

Protocols and materials databases

DNASU4208.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000340208; ENSP00000340874; ENSG00000081189. [Q06413-5]
ENST00000424173; ENSP00000389610; ENSG00000081189. [Q06413-6]
ENST00000437473; ENSP00000396219; ENSG00000081189. [Q06413-1]
ENST00000510942; ENSP00000422390; ENSG00000081189. [Q06413-2]
ENST00000514015; ENSP00000424606; ENSG00000081189. [Q06413-3]
ENST00000514028; ENSP00000426665; ENSG00000081189. [Q06413-1]
ENST00000539796; ENSP00000441153; ENSG00000081189. [Q06413-4]
GeneID4208.
KEGGhsa:4208.
UCSCuc003kji.2. human. [Q06413-2]
uc003kjj.3. human. [Q06413-1]
uc021ybh.1. human. [Q06413-4]

Organism-specific databases

CTD4208.
GeneCardsGC05M088051.
HGNCHGNC:6996. MEF2C.
HPAHPA005533.
MIM600662. gene.
613443. phenotype.
neXtProtNX_Q06413.
Orphanet228384. 5q14.3 microdeletion syndrome.
PharmGKBPA30734.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5068.
HOGENOMHOG000230620.
HOVERGENHBG053944.
InParanoidQ06413.
KOK04454.
OMAMQHSALS.
OrthoDBEOG793B7D.
PhylomeDBQ06413.
TreeFamTF314067.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
SignaLinkQ06413.

Gene expression databases

ArrayExpressQ06413.
BgeeQ06413.
CleanExHS_MEF2C.
GenevestigatorQ06413.

Family and domain databases

InterProIPR022102. HJURP_C.
IPR002100. TF_MADSbox.
[Graphical view]
PfamPF12347. HJURP_C. 1 hit.
PF00319. SRF-TF. 1 hit.
[Graphical view]
PRINTSPR00404. MADSDOMAIN.
SMARTSM00432. MADS. 1 hit.
[Graphical view]
SUPFAMSSF55455. SSF55455. 1 hit.
PROSITEPS00350. MADS_BOX_1. 1 hit.
PS50066. MADS_BOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMEF2C. human.
GeneWikiMEF2C.
GenomeRNAi4208.
NextBio16578.
PROQ06413.
SOURCESearch...

Entry information

Entry nameMEF2C_HUMAN
AccessionPrimary (citable) accession number: Q06413
Secondary accession number(s): C9JMZ0, D7F7N5, F8W7V7
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: July 9, 2014
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM