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Protein

Myocyte-specific enhancer factor 2A

Gene

MEF2A

Organism
Sus scrofa (Pig)
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)DescriptionActionsGraphical viewLength
DNA bindingi58 – 86Mef2-typeSequence analysisAdd BLAST29

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

Names & Taxonomyi

Protein namesi
Recommended name:
Myocyte-specific enhancer factor 2A
Gene namesi
Name:MEF2A
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Unplaced

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003669681 – 507Myocyte-specific enhancer factor 2AAdd BLAST507

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei59Phosphoserine; by CK2By similarity1
Modified residuei98PhosphoserineBy similarity1
Modified residuei235PhosphoserineBy similarity1
Modified residuei249N6-acetyllysineBy similarity1
Modified residuei255PhosphoserineBy similarity1
Modified residuei312Phosphothreonine; by MAPK7 and MAPK14By similarity1
Modified residuei319Phosphothreonine; by MAPK7 and MAPK14By similarity1
Modified residuei355Phosphoserine; by MAPK7By similarity1
Modified residuei403N6-acetyllysine; alternateBy similarity1
Cross-linki403Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Modified residuei408Phosphoserine; by CDK5By similarity1
Modified residuei415PhosphothreonineBy similarity1
Modified residuei453PhosphoserineBy similarity1

Post-translational modificationi

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 (By similarity).By similarity
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).By similarity
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 (By similarity).By similarity
Proteolytically cleaved on several sites by caspase 3 and caspase 7 following neurotoxicity. Preferentially cleaves the CDK5-mediated hyperphosphorylated form which leads to cortical neuron apoptosis and transcriptional inactivation (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei176 – 177CleavageCurated2
Sitei213 – 214CleavageCurated2
Sitei466 – 467CleavageCurated2

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiA2ICN5.

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

STRINGi9823.ENSSSCP00000026217.

Structurei

3D structure databases

ProteinModelPortaliA2ICN5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

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

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni266 – 283Required for interaction with MAPKsBy similarityAdd BLAST18
Regioni289 – 296Beta domainBy similarity8

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi256 – 259Poly-Pro4
Compositional biasi290 – 295Poly-Glu6
Compositional biasi420 – 448Gln/Pro-richAdd BLAST29
Compositional biasi457 – 464Poly-Ser8

Domaini

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

Sequence similaritiesi

Belongs to the MEF2 family.Curated
Contains 1 MADS-box domain.PROSITE-ProRule annotation
Contains 1 Mef2-type DNA-binding domain.Curated

Phylogenomic databases

eggNOGiKOG0014. Eukaryota.
COG5068. LUCA.
HOGENOMiHOG000230620.
HOVERGENiHBG053944.
InParanoidiA2ICN5.
KOiK09260.

Family and domain databases

CDDicd00265. MADS_MEF2_like. 1 hit.
InterProiIPR022102. HJURP_C.
IPR033896. MADS_MEF2-like.
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]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: A2ICN5-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGRKKIQITR IMDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNS
60 70 80 90 100
SNKLFQYAST DMDKVLLKYT EYNEPHESGT NSDIVEALNK KEHRGCDSPD
110 120 130 140 150
PDTSYVLTPH TEEKYKKINE EFDNMMRNHK IAPGLPPQNF SMSVTVPVTS
160 170 180 190 200
PNALSYTNPG SSLVSPSLAA SSTLADSSML SPPQATLHRN VSPGAPQRPP
210 220 230 240 250
STGSAGGMLS TSDLTVPNGA GSSPVGNGFV NSRASPNLVG TTGANSLGKV
260 270 280 290 300
MPTESPPPPG GGNLGMNSRK PDLRVVIPPS SKGMMPPLSE EEELELNTQR
310 320 330 340 350
ISSSQAPQPL ATPVVSVTTP SLPQQGLVYS AMPTAYNTDY SLTSADLSAL
360 370 380 390 400
QGFNSPGMLS LGQVSAWQQH HLGQAALSSL VAGGQLSQGS NLSINTNQNI
410 420 430 440 450
NIKSEPISPP RDRMTPSGFQ QQQPPPPSQA PQPQPPQPQP QPQPQARQEM
460 470 480 490 500
GRSPVDSLSS SSSSYDGSDR EDPRGDFHSP VVLGRPPNTE DRESPSVKRM

RMDAWVT
Length:507
Mass (Da):54,482
Last modified:March 24, 2009 - v2
Checksum:i0D84E0AB59A6C017
GO
Isoform 2 (identifier: A2ICN5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     227-260: Missing.

Show »
Length:473
Mass (Da):51,148
Checksum:i83E5509D6F5A526F
GO
Isoform 3 (identifier: A2ICN5-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     87-132: ALNKKEHRGC...DNMMRNHKIA → TLRKKGLNGC...DSDFIFKRGP
     227-260: Missing.

Show »
Length:471
Mass (Da):50,779
Checksum:i9225DCCE2610DF08
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti51S → T in ABM68043 (Ref. 1) Curated1
Sequence conflicti62M → I in ABM68043 (Ref. 1) Curated1
Sequence conflicti79G → R in ABQ53160 (Ref. 1) Curated1
Sequence conflicti179M → T in ABQ53159 (Ref. 1) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03659887 – 132ALNKK…NHKIA → TLRKKGLNGCESPDADDYFE HSPLSEDRFSKLNEDSDFIF KRGP in isoform 3. 1 PublicationAdd BLAST46
Alternative sequenceiVSP_036599227 – 260Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST34

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EF194143 mRNA. Translation: ABM68043.1.
EF576922 mRNA. Translation: ABQ53159.1.
EF576923 mRNA. Translation: ABQ53160.1.
RefSeqiNP_001090890.1. NM_001097421.1.
NP_001093168.1. NM_001099698.1. [A2ICN5-1]
UniGeneiSsc.19462.

Genome annotation databases

GeneIDi100037273.
KEGGissc:100037273.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EF194143 mRNA. Translation: ABM68043.1.
EF576922 mRNA. Translation: ABQ53159.1.
EF576923 mRNA. Translation: ABQ53160.1.
RefSeqiNP_001090890.1. NM_001097421.1.
NP_001093168.1. NM_001099698.1. [A2ICN5-1]
UniGeneiSsc.19462.

3D structure databases

ProteinModelPortaliA2ICN5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000026217.

Proteomic databases

PaxDbiA2ICN5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100037273.
KEGGissc:100037273.

Organism-specific databases

CTDi4205.

Phylogenomic databases

eggNOGiKOG0014. Eukaryota.
COG5068. LUCA.
HOGENOMiHOG000230620.
HOVERGENiHBG053944.
InParanoidiA2ICN5.
KOiK09260.

Family and domain databases

CDDicd00265. MADS_MEF2_like. 1 hit.
InterProiIPR022102. HJURP_C.
IPR033896. MADS_MEF2-like.
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...

Entry informationi

Entry nameiMEF2A_PIG
AccessioniPrimary (citable) accession number: A2ICN5
Secondary accession number(s): A5JUQ6, A5JUQ7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 24, 2009
Last sequence update: March 24, 2009
Last modified: November 30, 2016
This is version 62 of the entry and version 2 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.