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Q02078 (MEF2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Myocyte-specific enhancer factor 2A
Alternative name(s):
Serum response factor-like protein 1
Gene names
Name:MEF2A
Synonyms:MEF2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length507 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT]4TAR-3', found in numerous muscle-specific genes. Also involved in the activation of numerous 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. In cerebellar granule neurons, phosphorylated and sumoylated MEF2A represses transcription of NUR77 promoting synaptic differentiation. Associates with chromatin to the ZNF16 promoter. Ref.11 Ref.14 Ref.16 Ref.18 Ref.20 Ref.21 Ref.22 Ref.28

Subunit structure

Binds DNA as a homo- or heterodimer. Dimerizes with MEF2D. Interacts with HDAC7 By similarity. Interacts with PIAS1; the interaction enhances sumoylation. Interacts with HDAC4, HDAC9 and SLC2A4RG. Interacts (via the N-terminal) with MAPK7; the interaction results in the phosphorylation and transcriptional activity of MEF2A. Ref.1 Ref.9 Ref.10 Ref.11 Ref.12 Ref.17 Ref.20 Ref.33

Subcellular location

Nucleus Ref.16 Ref.20.

Tissue specificity

Isoform MEF2 and isoform MEFA are expressed only in skeletal and cardiac muscle and in the brain. Isoform RSRFC4 and isoform RSRFC9 are expressed in all tissues examined. Ref.1 Ref.3

Post-translational modification

Constitutive phosphorylation on Ser-408 promotes Lys-403 sumoylation thus preventing acetylation at this site. Dephosphorylation on Ser-408 by PPP3CA upon neuron depolarization promotes a switch from sumoylation to acetylation on residue Lys-403 leading to inhibition of dendrite claw differentiation. Phosphorylation on Thr-312 and Thr-319 are the main sites involved in p38 MAPK signaling and activate transcription. Phosphorylated on these sites by MAPK14/p38alpha and MAPK11/p38beta, but not by MAPK13/p38delta nor by MAPK12/p38gamma. Phosphorylation on Ser-408 by CDK5 induced by neurotoxicity inhibits MEF2A transcriptional activation leading to apoptosis of cortical neurons. Phosphorylation on Thr-312, Thr-319 and Ser-355 can be induced by EGF. Ref.9 Ref.11 Ref.12 Ref.13 Ref.15 Ref.16 Ref.19 Ref.21 Ref.22 Ref.23

Sumoylation on Lys-403 is enhanced by PIAS1 and represses transcriptional activity. Phosphorylation on Ser-408 is required for sumoylation. Has no effect on nuclear location nor on DNA binding. Sumoylated with SUMO1 and, to a lesser extent with SUMO2 and SUMO3. PIASx facilitates sumoylation in postsynaptic dendrites in the cerebellar cortex and promotes their morphogenesis By similarity. Ref.20 Ref.21

Acetylation on Lys-403 activates transcriptional activity. Acetylated by p300 on several sites in diffentiating myocytes. Acetylation on Lys-4 increases DNA binding and transactivation By similarity. Hyperacetylation by p300 leads to enhanced cardiac myocyte growth and heart failure. Ref.24

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. Ref.9 Ref.11 Ref.12 Ref.13 Ref.15 Ref.16 Ref.19 Ref.21 Ref.22 Ref.23

Involvement in disease

Coronary artery disease, autosomal dominant, 1 (ADCAD1) [MIM:608320]: A common heart disease characterized by reduced or absent blood flow in one or more of the arteries that encircle and supply the heart. Its most important complication is acute myocardial infarction.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Sequence similarities

Belongs to the MEF2 family.

Contains 1 MADS-box domain.

Contains 1 Mef2-type DNA-binding domain.

Sequence caution

The sequence AAH53871.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAD92222.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processApoptosis
Differentiation
Neurogenesis
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processERK5 cascade

Inferred from mutant phenotype PubMed 15132737. Source: UniProtKB

MAPK cascade

Inferred from direct assay Ref.11. 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

cardiac conduction

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to calcium ion

Inferred from direct assay Ref.22. Source: UniProtKB

dendrite morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

heart development

Inferred from expression pattern PubMed 10458488. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

mitochondrial genome maintenance

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrion distribution

Inferred from sequence or structural similarity. Source: UniProtKB

muscle cell differentiation

Traceable author statement. Source: Reactome

muscle organ development

Non-traceable author statement Ref.3. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.22. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of muscle cell differentiation

Traceable author statement. Source: Reactome

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 10748098PubMed 20590529Ref.28Ref.11. 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

transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 10748098Ref.22PubMed 20590529. Source: GOC

transcription, DNA-templated

Inferred from direct assay PubMed 16043483. Source: UniProtKB

ventricular cardiac myofibril assembly

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

nuclear chromatin

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

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.22PubMed 20590529. Source: UniProtKB

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

Inferred from electronic annotation. Source: Ensembl

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 PubMed 20590529. Source: UniProtKB

RNA polymerase II transcription coactivator activity

Inferred from direct assay PubMed 15466416. Source: BHF-UCL

RNA polymerase II transcription factor binding

Inferred from physical interaction PubMed 15466416. Source: BHF-UCL

SMAD binding

Inferred from physical interaction PubMed 11160896. Source: UniProtKB

activating transcription factor binding

Inferred from physical interaction PubMed 20590529. Source: UniProtKB

chromatin binding

Inferred from direct assay Ref.28. Source: UniProtKB

histone acetyltransferase binding

Inferred from physical interaction PubMed 20590529. Source: UniProtKB

histone deacetylase binding

Inferred from physical interaction PubMed 10748098PubMed 20590529. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 16043483. Source: BHF-UCL

protein heterodimerization activity

Inferred from physical interaction Ref.11. Source: UniProtKB

sequence-specific DNA binding

Inferred from direct assay Ref.32. Source: UniProtKB

sequence-specific DNA binding RNA polymerase II transcription factor activity

Inferred from direct assay PubMed 10748098Ref.22PubMed 20590529. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

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

Complete GO annotation...

Alternative products

This entry describes 8 isoforms produced by alternative splicing. [Align] [Select]
Isoform MEF2 (identifier: Q02078-1)

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 MEFA (identifier: Q02078-2)

The sequence of this isoform differs from the canonical sequence as follows:
     87-132: ALNKKEHRGC...DNMMRNHKIA → TLRKKGLNGC...DSDFIFKRGP
Isoform RSRFC4 (identifier: Q02078-3)

The sequence of this isoform differs from the canonical sequence as follows:
     289-296: Missing.
     420-421: Missing.
Isoform RSRFC9 (identifier: Q02078-4)

The sequence of this isoform differs from the canonical sequence as follows:
     87-132: ALNKKEHRGC...DNMMRNHKIA → TLRKKGLNGC...DSDFIFKRGP
     289-296: Missing.
     420-421: Missing.
Isoform 5 (identifier: Q02078-5)

The sequence of this isoform differs from the canonical sequence as follows:
     289-296: Missing.
Note: No experimental confirmation available.
Isoform 6 (identifier: Q02078-6)

The sequence of this isoform differs from the canonical sequence as follows:
     87-132: ALNKKEHRGC...DNMMRNHKIA → TLRKKGLNGC...DSDFIFKRGP
     289-296: Missing.
Note: No experimental confirmation available.
Isoform 7 (identifier: Q02078-7)

The sequence of this isoform differs from the canonical sequence as follows:
     19-86: Missing.
     87-132: ALNKKEHRGC...DNMMRNHKIA → TLRKKGLNGC...DSDFIFKRGP
Note: No experimental confirmation available. Contains a phosphoserine at position 30.
Isoform 8 (identifier: Q02078-8)

The sequence of this isoform differs from the canonical sequence as follows:
     19-62: VTFTKRKFGL...KLFQYASTDM → TLRKKGLNGC...DSDFIFKRGP
     63-132: Missing.
     289-296: Missing.
Note: No experimental confirmation available. Contains a phosphoserine at position 30.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 507507Myocyte-specific enhancer factor 2A
PRO_0000199428

Regions

Domain3 – 5755MADS-box
DNA binding58 – 8629Mef2-type Potential
Region266 – 28318Required for interaction with MAPKs
Region289 – 2968Beta domain
Compositional bias4 – 3128Lys-rich (basic)
Compositional bias141 – 18646Ser/Thr-rich
Compositional bias420 – 44627Gln/Pro-rich

Sites

Site176 – 1772Cleavage Probable
Site213 – 2142Cleavage Probable
Site466 – 4672Cleavage Probable

Amino acid modifications

Modified residue591Phosphoserine; by CK2 By similarity
Modified residue981Phosphoserine Ref.25
Modified residue2351Phosphoserine Ref.25
Modified residue2491N6-acetyllysine Ref.26
Modified residue2551Phosphoserine; by MAPK14 Ref.15 Ref.25
Modified residue3121Phosphothreonine; by MAPK7 and MAPK14; alternate Ref.11 Ref.12 Ref.13 Ref.15 Ref.23
Modified residue3121Phosphothreonine; by NLK; alternate Ref.11 Ref.12 Ref.13 Ref.15 Ref.23
Modified residue3191Phosphothreonine; by MAPK7 and MAPK14 Ref.11 Ref.12 Ref.13 Ref.15
Modified residue3551Phosphoserine; by MAPK7 Ref.13
Modified residue4031N6-acetyllysine; alternate By similarity
Modified residue4081Phosphoserine; by CDK5 Ref.15 Ref.16 Ref.21 Ref.22
Modified residue4531Phosphoserine; by MAPK Ref.11
Cross-link403Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate Ref.20 Ref.21

Natural variations

Alternative sequence19 – 8668Missing in isoform 7.
VSP_043338
Alternative sequence19 – 6244VTFTK…ASTDM → TLRKKGLNGCESPDADDYFE HSPLSEDRFSKLNEDSDFIF KRGP in isoform 8.
VSP_046018
Alternative sequence63 – 13270Missing in isoform 8.
VSP_046019
Alternative sequence87 – 13246ALNKK…NHKIA → TLRKKGLNGCESPDADDYFE HSPLSEDRFSKLNEDSDFIF KRGP in isoform MEFA, isoform RSRFC9, isoform 6 and isoform 7.
VSP_006240
Alternative sequence289 – 2968Missing in isoform RSRFC4, isoform RSRFC9, isoform 5, isoform 6 and isoform 8.
VSP_006241
Alternative sequence420 – 4212Missing in isoform RSRFC4 and isoform RSRFC9.
VSP_006242
Natural variant2631N → S. Ref.29
Corresponds to variant rs121918530 [ dbSNP | Ensembl ].
VAR_038407
Natural variant2791P → L. Ref.29 Ref.30 Ref.31
Corresponds to variant rs121918529 [ dbSNP | Ensembl ].
VAR_038408
Natural variant2831G → D. Ref.29
VAR_038409
Natural variant440 – 4467Missing Loss of nuclear localization; 66% decrease in transcription activation; loss of synergistic activation by MEF2A and GATA1 through a dominant-negative mechanism.
VAR_017743

Experimental info

Mutagenesis1761D → A: Abolishes cleavage at sites 1 and 2 by caspase 3. Increased cleavage at site 3 by caspase 3. Ref.14
Mutagenesis2131D → A: Abolishes cleavage at sites 2 and 3 by caspase 7. Ref.14
Mutagenesis2551S → A: Slightly increased MEF2A protein level. Ref.15
Mutagenesis2551S → D: Decreased MEF2A protein level. Ref.15
Mutagenesis2691R → A: Reduced p38 alpha- and beta2-mediated transcriptional activity; when associated with A-270. Ref.12
Mutagenesis2701K → A: Reduced p38 alpha- and beta2-mediated transcriptional activity; when associated with A-269. Ref.12
Mutagenesis2731L → A: Reduced p38 alpha- and beta2-mediated transcriptional activity; when associated with A-275. Ref.12
Mutagenesis2751V → A: Reduced p38 alpha- and beta2-mediated transcriptional activity; when associated with A-273. Ref.12
Mutagenesis2771I → A: Reduced p38 alpha- and beta2-mediated transcriptional activity; when associated with A-278. Ref.12
Mutagenesis2781P → A: Reduced p38 alpha- and beta2-mediated transcriptional activity; when associated with A-277. Ref.12
Mutagenesis3121T → A: Greatly reduced p38-mediated phosphorylation. Abolishes p38-mediated transcriptional activation; when associated with A-319. Ref.11 Ref.13
Mutagenesis3191T → A: Greatly reduced p38-mediated phosphorylation. Abolishes P38-mediated transcriptional activation; when associated with A-312. Ref.11 Ref.13
Mutagenesis3551S → A: No effect on p38-mediated transcriptional activity. Ref.11 Ref.13
Mutagenesis3871S → A: No effect on p38-mediated phosphorylation.
Mutagenesis4031K → R: Abolishes sumoylation. No change in subcellular location nor in DNA binding. Loss of transcriptional repression. Ref.20 Ref.21
Mutagenesis4081S → A: Loss of sumoylation. Ref.16 Ref.21
Mutagenesis4081S → D: Rescues sumoylation. Ref.16 Ref.21
Mutagenesis4531S → A: No effect on p38-mediated phosphorylation. Ref.11
Mutagenesis4791S → A: No effect on p38-mediated phosphorylation. Ref.11
Sequence conflict4301Missing in AAB17195. Ref.4
Sequence conflict4301Missing in AAB17196. Ref.4

Secondary structure

.............. 507
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform MEF2 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 362BA4FBCC792CE2

FASTA50754,811
        10         20         30         40         50         60 
MGRKKIQITR IMDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNS SNKLFQYAST 

        70         80         90        100        110        120 
DMDKVLLKYT EYNEPHESRT NSDIVEALNK KEHRGCDSPD PDTSYVLTPH TEEKYKKINE 

       130        140        150        160        170        180 
EFDNMMRNHK IAPGLPPQNF SMSVTVPVTS PNALSYTNPG SSLVSPSLAA SSTLTDSSML 

       190        200        210        220        230        240 
SPPQTTLHRN VSPGAPQRPP STGNAGGMLS TTDLTVPNGA GSSPVGNGFV NSRASPNLIG 

       250        260        270        280        290        300 
ATGANSLGKV MPTKSPPPPG GGNLGMNSRK PDLRVVIPPS SKGMMPPLSE EEELELNTQR 

       310        320        330        340        350        360 
ISSSQATQPL ATPVVSVTTP SLPPQGLVYS AMPTAYNTDY SLTSADLSAL QGFNSPGMLS 

       370        380        390        400        410        420 
LGQVSAWQQH HLGQAALSSL VAGGQLSQGS NLSINTNQNI SIKSEPISPP RDRMTPSGFQ 

       430        440        450        460        470        480 
QQQQQQQQQQ PPPPPQPQPQ PPQPQPRQEM GRSPVDSLSS SSSSYDGSDR EDPRGDFHSP 

       490        500 
IVLGRPPNTE DRESPSVKRM RMDAWVT 

« Hide

Isoform MEFA [UniParc].

Checksum: E0032FA6F955D7F7
Show »

FASTA50554,442
Isoform RSRFC4 [UniParc].

Checksum: A255A8EDC8B07FB0
Show »

FASTA49753,596
Isoform RSRFC9 [UniParc].

Checksum: 3C083C4EFC3872F0
Show »

FASTA49553,227
Isoform 5 [UniParc].

Checksum: FE3A83DDCE477C27
Show »

FASTA49953,852
Isoform 6 [UniParc].

Checksum: F4A61D805AE448AF
Show »

FASTA49753,483
Isoform 7 [UniParc].

Checksum: D28A536D0F0188BE
Show »

FASTA43746,529
Isoform 8 [UniParc].

Checksum: B356416F17385FCD
Show »

FASTA42945,570

References

« Hide 'large scale' references
[1]"Human SRF-related proteins: DNA-binding properties and potential regulatory targets."
Pollock R., Treisman R.
Genes Dev. 5:2327-2341(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS MEF2; RSRFC4 AND RSRFC9), DNA-BINDING, TISSUE SPECIFICITY, DIMERIZATION.
Tissue: Placenta.
[2]Treisman R.
Submitted (NOV-1993) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM RSRFC9), SEQUENCE REVISION.
[3]"Human myocyte-specific enhancer factor 2 comprises a group of tissue-restricted MADS box transcription factors."
Yu Y.-T., Breitbart R.E., Smoot L.B., Lee Y., Mahdavi V., Nadal-Ginard B.
Genes Dev. 6:1783-1798(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS MEF2 AND RSRFC9), TISSUE SPECIFICITY.
Tissue: Heart and Skeletal muscle.
[4]Suzuki E., Lowry J., Sonoda G., Testa J.R., Walsh K.
Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS RSRFC4 AND RSRFC9).
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7).
Tissue: Amygdala.
[6]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno F.R.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
Tissue: Brain.
[7]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 5 AND 8).
Tissue: Pancreas and Uterus.
[9]"Interaction of myocyte enhancer factor 2 (MEF2) with a mitogen-activated protein kinase, ERK5/BMK1."
Yang C.-C., Ornatsky O.I., McDermott J.C., Cruz T.F., Prody C.A.
Nucleic Acids Res. 26:4771-4777(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAPK7, PHOSPHORYLATION.
[10]"HDAC4 deacetylase associates with and represses the MEF2 transcription factor."
Miska E.A., Karlsson C., Langley E., Nielsen S.J., Pines J., Kouzarides T.
EMBO J. 18:5099-5107(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HDAC4 AND HDAC9.
[11]"Regulation of the MEF2 family of transcription factors by p38."
Zhao M., New L., Kravchenko V.V., Kato Y., Gram H., di Padova F., Olson E.N., Ulevitch R.J., Han J.-D.
Mol. Cell. Biol. 19:21-30(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-312; THR-319 AND SER-453, FUNCTION, HETERODIMERIZATION, MUTAGENESIS OF THR-312; THR-319; SER-355; SER-453 AND SER-479.
[12]"Targeting of p38 mitogen-activated protein kinases to MEF2 transcription factors."
Yang S.-H., Galanis A., Sharrocks A.D.
Mol. Cell. Biol. 19:4028-4038(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAPK14, PHOSPHORYLATION AT THR-312 AND THR-319, MUTAGENESIS OF ARG-269; LYS-270; LEU-273; VAL-275; ILE-277 AND PRO-278.
[13]"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 AT THR-312; THR-319 AND SER-355, MUTAGENESIS OF THR-312; THR-319 AND SER-355.
[14]"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-176; ASP-213 AND ASP-466, FUNCTION, MUTAGENESIS OF ASP-176 AND ASP-213.
[15]"Phosphorylation motifs regulating the stability and function of myocyte enhancer factor 2A."
Cox D.M., Du M., Marback M., Yang E.C.C., Chan J., Siu K.W.M., McDermott J.C.
J. Biol. Chem. 278:15297-15303(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-255; THR-312; THR-319 AND SER-408, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF SER-255.
[16]"Cdk5-mediated inhibition of the protective effects of transcription factor MEF2 in neurotoxicity-induced apoptosis."
Gong X., Tang X., Wiedmann M., Wang X., Peng J., Zheng D., Blair L.A.C., Marshall J., Mao Z.
Neuron 38:33-46(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-408, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-408.
[17]"Regulation of the human GLUT4 gene promoter: interaction between a transcriptional activator and myocyte enhancer factor 2A."
Knight J.B., Eyster C.A., Griesel B.A., Olson A.L.
Proc. Natl. Acad. Sci. U.S.A. 100:14725-14730(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SLC2A4RG.
[18]"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.
[19]"Cyclin-dependent kinase 5 mediates neurotoxin-induced degradation of the transcription factor myocyte enhancer factor 2."
Tang X., Wang X., Gong X., Tong M., Park D., Xia Z., Mao Z.
J. Neurosci. 25:4823-4834(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING, PHOSPHORYLATION.
[20]"SUMO-1 modification of MEF2A regulates its transcriptional activity."
Riquelme C., Barthel K.K., Liu X.
J. Cell. Mol. Med. 10:132-144(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION AT LYS-403, INTERACTION WITH PIAS1, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-403.
[21]"PDSM, a motif for phosphorylation-dependent SUMO modification."
Hietakangas V., Anckar J., Blomster H.A., Fujimoto M., Palvimo J.J., Nakai A., Sistonen L.
Proc. Natl. Acad. Sci. U.S.A. 103:45-50(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION AT LYS-403, PHOSPHORYLATION AT SER-408, FUNCTION, MUTAGENESIS OF LYS-403 AND SER-408.
[22]"A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation."
Shalizi A., Gaudilliere B., Yuan Z., Stegmueller J., Shirogane T., Ge Q., Tan Y., Schulman B., Harper J.W., Bonni A.
Science 311:1012-1017(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-408, FUNCTION.
[23]"Nemo-like kinase-myocyte enhancer factor 2A signaling regulates anterior formation in Xenopus development."
Satoh K., Ohnishi J., Sato A., Takeyama M., Iemura S., Natsume T., Shibuya H.
Mol. Cell. Biol. 27:7623-7630(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-312 BY NLK.
[24]"Quantitative control of adaptive cardiac hypertrophy by acetyltransferase p300."
Wei J.Q., Shehadeh L.A., Mitrani J.M., Pessanha M., Slepak T.I., Webster K.A., Bishopric N.H.
Circulation 118:934-946(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION, INVOLVEMENT IN CARDIAC HYPERTROPHY.
[25]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98; SER-235 AND SER-255, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-30 (ISOFORMS 7 AND 8), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[26]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-249, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[27]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]"Identification of HZF1 as a novel target gene of the MEF2 transcription factor."
Liu X., Jin E.Z., Zhi J.X., Li X.Q.
Mol. Med. Report. 4:465-469(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CHROMATIN BINDING.
[29]"Transcription factor MEF2A mutations in patients with coronary artery disease."
Bhagavatula M.R.K., Fan C., Shen G.-Q., Cassano J., Plow E.F., Topol E.J., Wang Q.
Hum. Mol. Genet. 13:3181-3188(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SER-263; LEU-279 AND ASP-283, CHARACTERIZATION OF VARIANTS SER-263; LEU-279 AND ASP-283.
[30]"The Pro279Leu variant in the transcription factor MEF2A is associated with myocardial infarction."
Gonzalez P., Garcia-Castro M., Reguero J.R., Batalla A., Ordonez A.G., Palop R.L., Lozano I., Montes M., Alvarez V., Coto E.
J. Med. Genet. 43:167-169(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LEU-279, ASSOCIATION WITH SUSCEPTIBILITY TO MYOCARDIAL INFARCTION.
[31]"Lack of association between the MEF2A gene and myocardial infarction."
Lieb W., Mayer B., Koenig I.R., Borwitzky I., Goetz A., Kain S., Hengstenberg C., Linsel-Nitschke P., Fischer M., Doering A., Wichmann H.E., Meitinger T., Kreutz R., Ziegler A., Schunkert H., Erdmann J.
Circulation 117:185-191(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LEU-279, LACK OF ASSOCIATION WITH MYOCARDIAL INFARCTION.
[32]"Solution structure of the MEF2A-DNA complex: structural basis for the modulation of DNA bending and specificity by MADS-box transcription factors."
Huang K., Louis J.M., Donaldson L., Lim F.L., Sharrocks A.D., Clore G.M.
EMBO J. 19:2615-2628(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 2-86 IN COMPLEX WITH DNA.
[33]"Crystal structure of MEF2A core bound to DNA at 1.5 A resolution."
Santelli E., Richmond T.J.
J. Mol. Biol. 297:437-449(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 2-78 IN COMPLEX WITH DNA, DIMERIZATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y16312 mRNA. Translation: CAA76175.1.
X63381 mRNA. Translation: CAA44979.1.
X68503 mRNA. Translation: CAA48516.1.
X68505 mRNA. Translation: CAA48517.1.
U49020 expand/collapse EMBL AC list , U44889, U49012, U49013, U49015, U49016, U49017, U49018, U49019 Genomic DNA. Translation: AAB17195.1.
U49020 expand/collapse EMBL AC list , U44889, U49012, U49013, U49015, U49016, U49017, U49018, U49019 Genomic DNA. Translation: AAB17196.1.
AK294207 mRNA. Translation: BAG57518.1.
AB208985 mRNA. Translation: BAD92222.1. Different initiation.
AC015660 Genomic DNA. No translation available.
AC022692 Genomic DNA. No translation available.
AC103967 Genomic DNA. No translation available.
BC013437 mRNA. Translation: AAH13437.1.
BC053871 mRNA. Translation: AAH53871.1. Different initiation.
CCDSCCDS45362.1. [Q02078-5]
CCDS45363.1. [Q02078-7]
CCDS53978.1. [Q02078-6]
CCDS58401.1. [Q02078-8]
PIRC39481.
S25831.
RefSeqNP_001124398.1. NM_001130926.1. [Q02078-6]
NP_001124399.1. NM_001130927.1. [Q02078-7]
NP_001124400.1. NM_001130928.1. [Q02078-8]
NP_001165365.1. NM_001171894.1. [Q02078-6]
NP_005578.2. NM_005587.2. [Q02078-5]
XP_005254972.1. XM_005254915.1. [Q02078-6]
UniGeneHs.268675.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1C7UNMR-A/B2-86[»]
1EGWX-ray1.50A/B/C/D2-78[»]
1LEWX-ray2.30A223-226[»]
3KOVX-ray2.90A/B/I/J2-91[»]
3MU6X-ray2.43A/B/C/D2-70[»]
3P57X-ray2.19A/B/C/D/I/J2-91[»]
ProteinModelPortalQ02078.
SMRQ02078. Positions 2-91.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110369. 26 interactions.
DIPDIP-40711N.
IntActQ02078. 9 interactions.
MINTMINT-104848.
STRING9606.ENSP00000346389.

PTM databases

PhosphoSiteQ02078.

Proteomic databases

MaxQBQ02078.
PaxDbQ02078.
PRIDEQ02078.

Protocols and materials databases

DNASU4205.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000354410; ENSP00000346389; ENSG00000068305. [Q02078-5]
ENST00000449277; ENSP00000399460; ENSG00000068305. [Q02078-8]
ENST00000453228; ENSP00000404110; ENSG00000068305. [Q02078-6]
ENST00000557785; ENSP00000453441; ENSG00000068305. [Q02078-6]
ENST00000557942; ENSP00000453095; ENSG00000068305. [Q02078-2]
ENST00000558812; ENSP00000454120; ENSG00000068305. [Q02078-7]
GeneID4205.
KEGGhsa:4205.
UCSCuc002bve.3. human. [Q02078-2]
uc002bvf.3. human. [Q02078-5]
uc002bvg.3. human. [Q02078-6]
uc010urv.2. human. [Q02078-7]
uc010urw.2. human. [Q02078-1]

Organism-specific databases

CTD4205.
GeneCardsGC15P100107.
H-InvDBHIX0012611.
HGNCHGNC:6993. MEF2A.
HPACAB004499.
HPA046597.
HPA056563.
MIM600660. gene.
608320. phenotype.
neXtProtNX_Q02078.
PharmGKBPA30731.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5068.
HOGENOMHOG000230620.
HOVERGENHBG053944.
InParanoidQ02078.
KOK09260.
PhylomeDBQ02078.
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.
SignaLinkQ02078.

Gene expression databases

ArrayExpressQ02078.
BgeeQ02078.
CleanExHS_MEF2A.
GenevestigatorQ02078.

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

EvolutionaryTraceQ02078.
GeneWikiMyocyte-specific_enhancer_factor_2A.
GenomeRNAi4205.
NextBio16568.
PMAP-CutDBQ02078.
PROQ02078.
SOURCESearch...

Entry information

Entry nameMEF2A_HUMAN
AccessionPrimary (citable) accession number: Q02078
Secondary accession number(s): B4DFQ7 expand/collapse secondary AC list , F6XG23, O43814, Q14223, Q14224, Q59GX4, Q7Z6C9, Q96D14
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 9, 2014
This is version 149 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM