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Protein

Myocyte-specific enhancer factor 2A

Gene

MEF2A

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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).By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi58 – 8629Mef2-typeSequence analysisAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Apoptosis, Differentiation, Neurogenesis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-BTA-375170. CDO in myogenesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Myocyte-specific enhancer factor 2A
Gene namesi
Name:MEF2A
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 21

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 492492Myocyte-specific enhancer factor 2APRO_0000366967Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei59 – 591Phosphoserine; by CK2By similarity
Modified residuei98 – 981PhosphoserineBy similarity
Modified residuei235 – 2351PhosphoserineBy similarity
Modified residuei249 – 2491N6-acetyllysineBy similarity
Modified residuei255 – 2551PhosphoserineBy similarity
Modified residuei304 – 3041Phosphothreonine; by MAPK7 and MAPK14By similarity
Modified residuei311 – 3111Phosphothreonine; by MAPK7 and MAPK14By similarity
Modified residuei347 – 3471Phosphoserine; by MAPK7By similarity
Modified residuei395 – 3951N6-acetyllysine; alternateBy similarity
Cross-linki395 – 395Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Modified residuei400 – 4001Phosphoserine; by CDK5By similarity
Modified residuei407 – 4071PhosphothreonineBy similarity
Modified residuei438 – 4381Phosphoserine; by MAPKBy similarity

Post-translational modificationi

Constitutive phosphorylation on Ser-400 promotes Lys-395 sumoylation thus preventing acetylation at this site. Dephosphorylation on Ser-400 by PPP3CA upon neuron depolarization promotes a switch from sumoylation to acetylation on residue Lys-395 leading to inhibition of dendrite claw differentiation. Phosphorylation on Thr-304 and Thr-311 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-400 by CDK5 induced by neurotoxicity inhibits MEF2A transcriptional activation leading to apoptosis of cortical neurons. Phosphorylation on Thr-304, Thr-311 and Ser-347 can be induced by EGF (By similarity).By similarity
Sumoylation on Lys-395 is enhanced by PIAS1 and represses transcriptional activity. Phosphorylation on Ser-400 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).By similarity
Acetylation on Lys-395 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 (By similarity).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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei176 – 1772CleavageCurated
Sitei213 – 2142CleavageCurated
Sitei451 – 4522CleavageCurated

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiA2VDZ3.

Interactioni

Subunit structurei

Binds DNA as a homo- or heterodimer (By similarity). 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).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000014074.

Structurei

3D structure databases

ProteinModelPortaliA2VDZ3.
SMRiA2VDZ3. Positions 2-73.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini3 – 5755MADS-boxPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni266 – 28318Required for interaction with MAPKsBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi256 – 2594Poly-Pro
Compositional biasi412 – 43322Gln/Pro-richAdd
BLAST
Compositional biasi442 – 4498Poly-Ser

Sequence similaritiesi

Contains 1 MADS-box domain.PROSITE-ProRule annotation
Contains 1 Mef2-type DNA-binding domain.Curated

Phylogenomic databases

eggNOGiKOG0014. Eukaryota.
COG5068. LUCA.
GeneTreeiENSGT00390000011828.
HOVERGENiHBG053944.
InParanoidiA2VDZ3.
KOiK09260.
OMAiPATLHRN.
OrthoDBiEOG793B7D.
TreeFamiTF314067.

Family and domain databases

InterProiIPR022102. HJURP_C.
IPR002100. TF_MADSbox.
[Graphical view]
PfamiPF12347. HJURP_C. 1 hit.
PF00319. SRF-TF. 1 hit.
[Graphical view]
PRINTSiPR00404. MADSDOMAIN.
SMARTiSM00432. MADS. 1 hit.
[Graphical view]
SUPFAMiSSF55455. SSF55455. 1 hit.
PROSITEiPS00350. MADS_BOX_1. 1 hit.
PS50066. MADS_BOX_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

A2VDZ3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRKKIQITR IMDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNS
60 70 80 90 100
SNKLFQYAST DMDKVLLKYT EYNEPHESRT NSDIVEALNK KEHRGCDSPD
110 120 130 140 150
PDTSYVLTPH TEEKYKKINE EFDNMMRNHK IAPGLPPQNF SMSVTVPVTS
160 170 180 190 200
PSALSYTNPG SSLVSPSLAA SSALADTSML SPPQATLHRN VSPGAPQRPP
210 220 230 240 250
STGSAGGMLS TSDLTVPNGA GSSPVGNGFV NSRASPNLIG TTGANSLGKV
260 270 280 290 300
MPTKSPPPPG GGSLGMNSRK PDLRVVIPPS SKGMMPPLNT QRISSSQATQ
310 320 330 340 350
PLATPVVSVT TPSLPPQGLV YSAMPTAYNT DYSLTSADLS ALQGFNSPGM
360 370 380 390 400
LSLGQVSAWQ QHHLGQAALN SLVAGGQLSQ GSNLSINTNQ NINIKSEPIS
410 420 430 440 450
PPRDRMTPSG FQQQQQPQPP PPPPQAPQPQ PRQEVGRSPV DSLSSSSSSY
460 470 480 490
DGSDREDPRG DFHSPVVLGR PPNSEDRESP SVKRMRMDAW VT
Length:492
Mass (Da):52,782
Last modified:March 20, 2007 - v1
Checksum:i28A7A04D9E02A054
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC133487 mRNA. Translation: AAI33488.1.
RefSeqiNP_001077107.1. NM_001083638.2.
UniGeneiBt.25066.

Genome annotation databases

EnsembliENSBTAT00000014074; ENSBTAP00000014074; ENSBTAG00000010649.
GeneIDi407231.
KEGGibta:407231.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC133487 mRNA. Translation: AAI33488.1.
RefSeqiNP_001077107.1. NM_001083638.2.
UniGeneiBt.25066.

3D structure databases

ProteinModelPortaliA2VDZ3.
SMRiA2VDZ3. Positions 2-73.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000014074.

Proteomic databases

PaxDbiA2VDZ3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000014074; ENSBTAP00000014074; ENSBTAG00000010649.
GeneIDi407231.
KEGGibta:407231.

Organism-specific databases

CTDi4205.

Phylogenomic databases

eggNOGiKOG0014. Eukaryota.
COG5068. LUCA.
GeneTreeiENSGT00390000011828.
HOVERGENiHBG053944.
InParanoidiA2VDZ3.
KOiK09260.
OMAiPATLHRN.
OrthoDBiEOG793B7D.
TreeFamiTF314067.

Enzyme and pathway databases

ReactomeiR-BTA-375170. CDO in myogenesis.

Family and domain databases

InterProiIPR022102. HJURP_C.
IPR002100. TF_MADSbox.
[Graphical view]
PfamiPF12347. HJURP_C. 1 hit.
PF00319. SRF-TF. 1 hit.
[Graphical view]
PRINTSiPR00404. MADSDOMAIN.
SMARTiSM00432. MADS. 1 hit.
[Graphical view]
SUPFAMiSSF55455. SSF55455. 1 hit.
PROSITEiPS00350. MADS_BOX_1. 1 hit.
PS50066. MADS_BOX_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. NIH - Mammalian Gene Collection (MGC) project
    Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Thymus.

Entry informationi

Entry nameiMEF2A_BOVIN
AccessioniPrimary (citable) accession number: A2VDZ3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 24, 2009
Last sequence update: March 20, 2007
Last modified: June 8, 2016
This is version 69 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

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