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Q60929 (MEF2A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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 2A
Gene names
Name:Mef2a
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length498 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 By similarity.

Subunit structure

Binds DNA as a homo- or heterodimer. Dimerizes with MEF2D. Interacts with HDAC7. 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 By similarity. Ref.4 Ref.6

Subcellular location

Nucleus.

Tissue specificity

Widely expressed though mainly restricted to skeletal and cardiac muscle, brain, neurons and lymphocytes. Differentially expressed depending on if isoforms contain the beta domain or not, with the total expression of the beta domain-lacking isoforms vastly exceding that of the beta domain-containing isoforms. Isoforms containing the beta domain are expressed primarily in skeletal and cardiac muscle and in brain. Also present in lung and testis. Splicing to include the beta domain is induced in differentiating myocytes. Isoforms lacking the beta domain are expressed less abundantly in skeletal muscle, brain and lymphocytes, and are uniquely found in ovary, liver, spleen and kidney. In embryos, the beta domain-containing and beta domain-lacking isoforms are equally expressed. Also expressed cerebellar granule neurons and other regions of the CNS. Highest levels in the olfactory bulb, cortex, hippocampus, thalamus and cerebellum. Ref.1 Ref.5

Developmental stage

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

Domain

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

Post-translational modification

Constitutive phosphorylation on Ser-406 promotes Lys-401 sumoylation thus preventing acetylation at this site. Dephosphorylation on Ser-406 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 By similarity. Isoform 3 is phosphorylated on Ser-98 and Thr-108. Ref.6

Sumoylation on Lys-401 is enhanced by PIAS1 and represses transcriptional activity. Phosphorylation on Ser-406 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.

Acetylation on Lys-401 activates transcriptional activity. Acetylated by p300 on several sites in diffentiating myocytes. Acetylation on Lys-4 increases DNA binding and transactivation. Hyperacetylation by p300 leads to enhanced cardiac myocyte growth and heart failure By similarity.

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 By similarity. Ref.6

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
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processERK5 cascade

Inferred from sequence or structural similarity. Source: UniProtKB

MAPK cascade

Inferred from sequence or structural similarity. Source: UniProtKB

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cardiac conduction

Inferred from mutant phenotype PubMed 12379849. Source: UniProtKB

cellular response to calcium ion

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrial genome maintenance

Inferred from mutant phenotype PubMed 12379849. Source: UniProtKB

mitochondrion distribution

Inferred from mutant phenotype PubMed 12379849. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

nervous system development

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 20399744PubMed 8900141. Source: MGI

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12097321. Source: MGI

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12130539PubMed 9738004. Source: MGI

ventricular cardiac myofibril assembly

Inferred from mutant phenotype PubMed 12379849. Source: UniProtKB

   Cellular_componentnuclear chromatin

Inferred from direct assay PubMed 20833138. Source: BHF-UCL

nucleus

Inferred from direct assay PubMed 11160896. Source: UniProtKB

   Molecular_functionDNA binding

Inferred from direct assay PubMed 15491989PubMed 9738004. Source: MGI

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 16407236. Source: MGI

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

Inferred from direct assay PubMed 21379568. Source: MGI

RNA polymerase II regulatory region sequence-specific DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

RNA polymerase II transcription coactivator activity

Inferred from electronic annotation. Source: Ensembl

SMAD binding

Inferred from sequence or structural similarity. Source: UniProtKB

activating transcription factor binding

Inferred from physical interaction PubMed 11160896. Source: UniProtKB

chromatin binding

Inferred from direct assay PubMed 16407236PubMed 18198354PubMed 21379568. Source: MGI

histone acetyltransferase binding

Inferred from sequence or structural similarity. Source: UniProtKB

histone deacetylase binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein kinase binding

Inferred from physical interaction Ref.6. Source: UniProtKB

sequence-specific DNA binding

Inferred from direct assay PubMed 8096811. Source: MGI

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 12130539PubMed 9738004. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

NfixP70257-22EBI-2639094,EBI-2639084

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q60929-1)

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: Q60929-2)

The sequence of this isoform differs from the canonical sequence as follows:
     287-294: Missing.
Isoform 3 (identifier: Q60929-3)

The sequence of this isoform differs from the canonical sequence as follows:
     87-130: TLRKKGLNGC...DSDFIFKRGP → ALNKKEHRGC...DNMMRNHKIA
     287-294: Missing.
Note: Contains a phosphoserine at position 98. Contains a phosphothreonine at position 108.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 498498Myocyte-specific enhancer factor 2A
PRO_0000199429

Regions

Domain3 – 5755MADS-box
DNA binding58 – 8629Mef2-type Potential
Region264 – 28118Required for interaction with MAPKs By similarity
Region287 – 2948Beta domain By similarity
Compositional bias254 – 2574Poly-Pro
Compositional bias288 – 2936Poly-Glu
Compositional bias418 – 43922Gln/Pro-rich
Compositional bias448 – 4558Poly-Ser

Sites

Site174 – 1752Cleavage Probable
Site211 – 2122Cleavage Probable
Site457 – 4582Cleavage Probable

Amino acid modifications

Modified residue591Phosphoserine; by CK2 By similarity
Modified residue981Phosphoserine By similarity
Modified residue2331Phosphoserine By similarity
Modified residue2471N6-acetyllysine Ref.8
Modified residue2531Phosphoserine By similarity
Modified residue3101Phosphothreonine; by MAPK7; alternate By similarity
Modified residue3101Phosphothreonine; by NLK; alternate Ref.6
Modified residue3171Phosphothreonine; by MAPK7 By similarity
Modified residue3531Phosphoserine; by MAPK7 By similarity
Modified residue4011N6-acetyllysine; alternate By similarity
Modified residue4061Phosphoserine By similarity
Modified residue4441Phosphoserine By similarity
Cross-link401Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate By similarity

Natural variations

Alternative sequence87 – 13044TLRKK…FKRGP → ALNKKEHRGCDSPDPDTSYV LTPHTEEKYKKINEEFDNMM RNHKIA in isoform 3.
VSP_026060
Alternative sequence287 – 2948Missing in isoform 2 and isoform 3.
VSP_026031

Experimental info

Sequence conflict981S → N in AAA74030. Ref.1
Sequence conflict1161S → I in AAA74030. Ref.1
Sequence conflict1331L → F in AAA74030. Ref.1
Sequence conflict1511A → P in AAA74030. Ref.1
Sequence conflict1541Y → D in AAA74030. Ref.1
Sequence conflict174 – 1752DS → ET in AAA74030. Ref.1
Sequence conflict2011G → S in BAE21297. Ref.2
Sequence conflict2741V → A in AAA74030. Ref.1
Sequence conflict3671Q → E in AAA74030. Ref.1
Sequence conflict373 – 3742AA → TT in AAA74030. Ref.1
Sequence conflict419 – 4235QQQQQ → HHHHH in AAA74030. Ref.1
Sequence conflict4781P → A in AAA74030. Ref.1

Sequences

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

Last modified May 29, 2007. Version 2.
Checksum: FE291C3E3E0A5E70

FASTA49853,579
        10         20         30         40         50         60 
MGRKKIQITR IMDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNS SNKLFQYAST 

        70         80         90        100        110        120 
DMDKVLLKYT EYNEPHESRT NSDIVETLRK KGLNGCESPD ADDYFEHSPL SEDRFSKLNE 

       130        140        150        160        170        180 
DSDFIFKRGP PGLPPQNFSM SVTVPVTSPN ALSYTNPGSS LVSPSLAASS TLADSSMLSP 

       190        200        210        220        230        240 
PPATLHRNVS PGAPQRPPST GSASGMLSTT DLTVPNGAGN SPVGNGFVNS RASPNLIGNT 

       250        260        270        280        290        300 
GANSLGKVMP TKSPPPPGGG SLGMNSRKPD LRVVIPPSSK GMMPPLSEEE ELELNAQRIS 

       310        320        330        340        350        360 
SSQATQPLAT PVVSVTTPSL PPQGLVYSAM PTAYNTDYSL TSADLSALQG FTSPGMLSLG 

       370        380        390        400        410        420 
QASAWQQHHL GQAALSSLVA GGQLSQGSNL SINTNQNINI KSEPISPPRD RMTPSGFQQQ 

       430        440        450        460        470        480 
QQQPQQQPPP QPPQPQPRQE MGRSPVDSLS SSSSSYDGSD REDPRGDFHS PIVLGRPPNT 

       490 
EDRESPSVKR MRMDTWVT 

« Hide

Isoform 2 [UniParc].

Checksum: 2E15C204F58A9646
Show »

FASTA49052,620
Isoform 3 [UniParc].

Checksum: 961882F1C572ACCF
Show »

FASTA49252,990

References

« Hide 'large scale' references
[1]"The expression of MEF2 genes is implicated in CNS neuronal differentiation."
Lin X., Shah S., Bulleit R.F.
Brain Res. Mol. Brain Res. 42:307-316(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
Tissue: Cerebellum.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Strain: C57BL/6J.
Tissue: Testis.
[3]"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 1 AND 3).
Strain: NMRI.
Tissue: Brain and Mammary tumor.
[4]"Mechanism for nucleocytoplasmic shuttling of histone deacetylase 7."
Kao H.-Y., Verdel A., Tsai C.-C., Simon C., Juguilon H., Khochbin S.
J. Biol. Chem. 276:47496-47507(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HDAC7.
[5]"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: TISSUE SPECIFICITY OF ISOFORMS.
[6]"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: INTERACTION WITH NLK, PHOSPHORYLATION AT THR-310.
[7]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98 AND THR-108 (ISOFORM 3), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[8]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-247, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U30823 mRNA. Translation: AAA74030.1.
AK132678 mRNA. Translation: BAE21297.1.
BC061128 mRNA. Translation: AAH61128.1.
BC096598 mRNA. Translation: AAH96598.1.
RefSeqNP_001028885.1. NM_001033713.1.
XP_006540749.1. XM_006540686.1.
XP_006540750.1. XM_006540687.1.
XP_006540751.1. XM_006540688.1.
XP_006540752.1. XM_006540689.1.
UniGeneMm.132788.
Mm.491250.

3D structure databases

ProteinModelPortalQ60929.
SMRQ60929. Positions 2-73.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201381. 3 interactions.
IntActQ60929. 2 interactions.
MINTMINT-3155471.
STRING10090.ENSMUSP00000117496.

PTM databases

PhosphoSiteQ60929.

Proteomic databases

PaxDbQ60929.
PRIDEQ60929.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000032776; ENSMUSP00000032776; ENSMUSG00000030557. [Q60929-3]
ENSMUST00000076325; ENSMUSP00000075664; ENSMUSG00000030557. [Q60929-3]
ENSMUST00000107476; ENSMUSP00000103100; ENSMUSG00000030557. [Q60929-2]
ENSMUST00000135493; ENSMUSP00000138566; ENSMUSG00000030557. [Q60929-1]
ENSMUST00000156690; ENSMUSP00000117496; ENSMUSG00000030557. [Q60929-1]
GeneID17258.
KEGGmmu:17258.
UCSCuc009hif.2. mouse. [Q60929-1]
uc009hih.2. mouse. [Q60929-2]
uc009hii.2. mouse. [Q60929-3]

Organism-specific databases

CTD4205.
MGIMGI:99532. Mef2a.

Phylogenomic databases

eggNOGCOG5068.
GeneTreeENSGT00390000011828.
HOGENOMHOG000230620.
HOVERGENHBG053944.
InParanoidQ60929.
KOK09260.
OMARMDTWVT.
OrthoDBEOG793B7D.
TreeFamTF314067.

Gene expression databases

ArrayExpressQ60929.
BgeeQ60929.
CleanExMM_MEF2A.
GenevestigatorQ60929.

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

ChiTaRSMEF2A. mouse.
NextBio291742.
PROQ60929.
SOURCESearch...

Entry information

Entry nameMEF2A_MOUSE
AccessionPrimary (citable) accession number: Q60929
Secondary accession number(s): Q3V155, Q4VA09, Q6P8Q3
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 29, 2007
Last modified: April 16, 2014
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot