Reactome | UniProt:Q02078 MEF2A

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UniProt:Q02078 MEF2A Show undefined attributes

chain	chain:1-507
checksum	362BA4FBCC792CE2
comment	FUNCTION Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-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.SUBUNIT 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.INTERACTION 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.PTM 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.PTM 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).PTM 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.PTM 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.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the MEF2 family.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Extended N-terminus.
crossReference	[DatabaseIdentifier:10974863] Pharos - Targets:Q02078 [DatabaseIdentifier:11071836] OpenTargets:ENSG00000068305 [DatabaseIdentifier:11596750] RefSeq:NP_001124399.1 [DatabaseIdentifier:11596755] RefSeq:NP_001124400.1 [DatabaseIdentifier:11596766] RefSeq:NP_001165365.1 [DatabaseIdentifier:11596771] RefSeq:NP_001306135.1 [DatabaseIdentifier:11596781] RefSeq:NP_005578.2 [DatabaseIdentifier:11596785] RefSeq:XP_011519883.1 [DatabaseIdentifier:11596793] RefSeq:XP_011519884.1 [DatabaseIdentifier:11596797] RefSeq:XP_011519888.1 [DatabaseIdentifier:11596805] RefSeq:XP_016877679.1 [DatabaseIdentifier:11596809] RefSeq:XP_016877680.1 [DatabaseIdentifier:11596817] RefSeq:XP_016877682.1 [DatabaseIdentifier:11596821] RefSeq:XP_016877683.1 [DatabaseIdentifier:11706420] PDB:1C7U [DatabaseIdentifier:11706435] PDB:1EGW [DatabaseIdentifier:11706450] PDB:1LEW [DatabaseIdentifier:11706464] PDB:3KOV [DatabaseIdentifier:11706478] PDB:3MU6 [DatabaseIdentifier:11706499] PDB:3P57 [DatabaseIdentifier:11706514] PDB:6BYY [DatabaseIdentifier:11706528] PDB:6BZ1 [DatabaseIdentifier:11828816] PRO:Q02078 [DatabaseIdentifier:11851870] GeneCards:Q02078 [DatabaseIdentifier:11883958] Orphanet:23149 [DatabaseIdentifier:11900642] HPA:ENSG00000068305-MEF2A [DatabaseIdentifier:12170929] Ensembl:ENSP00000509537 [DatabaseIdentifier:12170930] Ensembl:ENST00000354410 [DatabaseIdentifier:12170931] Ensembl:ENSP00000509137 [DatabaseIdentifier:12170932] Ensembl:ENST00000686611 [DatabaseIdentifier:12170933] Ensembl:ENSG00000068305 [DatabaseIdentifier:12170934] Ensembl:ENST00000449277 [DatabaseIdentifier:12170935] Ensembl:ENSP00000454120 [DatabaseIdentifier:12170936] Ensembl:ENST00000557785 [DatabaseIdentifier:12170937] Ensembl:ENST00000558812 [DatabaseIdentifier:12170938] Ensembl:ENSP00000453095 [DatabaseIdentifier:12170939] Ensembl:ENST00000557942 [DatabaseIdentifier:12170940] Ensembl:ENSP00000453441 [DatabaseIdentifier:12170941] Ensembl:ENSP00000346389 [DatabaseIdentifier:12170942] Ensembl:ENST00000691492 [DatabaseIdentifier:12170943] Ensembl:ENSP00000399460
databaseName	UniProt
dbId	59133
description	recommendedName: Myocyte-specific enhancer factor 2A alternativeName: Serum response factor-like protein 1
displayName	UniProt:Q02078 MEF2A
geneName	MEF2A MEF2
identifier	Q02078
isSequenceChanged	false
keyword	3D-structure Acetylation Activator Alternative splicing Apoptosis Developmental protein Differentiation Disease variant DNA-binding Isopeptide bond Neurogenesis Nucleus Phosphoprotein Reference proteome Transcription Transcription regulation Ubl conjugation
modified	[InstanceEdit:12187927] Wright, Adam, 2024-03-12
name	MEF2A
otherIdentifier	11718096_a_at 11718097_a_at 11724863_a_at 11735491_a_at 16805594 208328_PM_s_at 208328_s_at 212535_PM_at 212535_at 214684_3p_at 214684_PM_at 214684_at 3611172 3611173 3611174 3611175 3611176 3611177 3611189 3611198 3611199 3611201 3611219 3611221 3611222 3611223 3611229 3611230 3611247 3611250 3611251 3611255 3611256 3611257 3611258 3611259 3611260 3611261 3611262 3611263 3611264 41747_s_at 4205 44865_s_at 7986411 A_14_P133989 A_23_P353652 A_24_P1731 A_33_P3341676 GE81532 GO:0000002 GO:0000122 GO:0000165 GO:0000785 GO:0000977 GO:0000978 GO:0000981 GO:0001228 GO:0003012 GO:0003013 GO:0003677 GO:0003682 GO:0003700 GO:0005515 GO:0005634 GO:0005654 GO:0005667 GO:0005694 GO:0005829 GO:0006351 GO:0006355 GO:0006915 GO:0007005 GO:0007010 GO:0007399 GO:0007507 GO:0007517 GO:0010613 GO:0010628 GO:0012501 GO:0019901 GO:0023052 GO:0030154 GO:0035035 GO:0042826 GO:0043226 GO:0043229 GO:0043565 GO:0045893 GO:0045944 GO:0046326 GO:0046332 GO:0046982 GO:0046983 GO:0048311 GO:0048513 GO:0048813 GO:0048856 GO:0055005 GO:0055085 GO:0061337 GO:0061629 GO:0070375 GO:0071277 GO:0140110 GO:0140297 HMNXSV003023441 HMNXSV003026888 Hs.182280.2.S1_3p_at Hs.182280.2.S1_3p_x_at Hs.288993.0.A1_3p_at ILMN_1661888 PH_hs_0025001 TC15000955.hg TC15002404.hg U49020_cds2_s_at X68505_s_at g5031906_3p_a_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-448834] p-T312,T319-MEF2A [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-199909] p-S408-MEF2A [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-199903] MEF2A [nucleoplasm] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8994938] ENSEMBL:ENSG00000068305 MEF2A [ReferenceDNASequence:11030907] KEGG Gene (Homo sapiens):4205 MEF2A [ReferenceDNASequence:11233210] NCBI Gene:4205 MEF2A [ReferenceDNASequence:11233211] BioGPS Gene:4205 MEF2A [ReferenceDNASequence:11233212] CTD Gene:4205 MEF2A [ReferenceDNASequence:11233213] dbSNP Gene:4205 MEF2A [ReferenceDNASequence:11233214] Monarch:4205 MEF2A [ReferenceDNASequence:11350529] ENSEMBL_homo_sapiens_GENE:ENSG00000068305.19 MEF2A [ReferenceDNASequence:11510328] UCSC:Q02078 MEF2A [ReferenceDNASequence:11797534] OMIM:600660 MEF2A [ReferenceDNASequence:11879216] HGNC:6993 MEF2A [ReferenceDNASequence:12196691] COSMIC (genes):MEF2A MEF2A
referenceTranscript	[ReferenceRNASequence:11441008] RefSeq:NM_001130927.2 MEF2A [ReferenceRNASequence:11441014] RefSeq:NM_001130928.2 MEF2A [ReferenceRNASequence:11441022] RefSeq:NM_001171894.2 MEF2A [ReferenceRNASequence:11441028] RefSeq:NM_001319206.1 MEF2A [ReferenceRNASequence:11441036] RefSeq:NM_005587.3 MEF2A [ReferenceRNASequence:11441043] RefSeq:XM_011521581.2 MEF2A [ReferenceRNASequence:11441051] RefSeq:XM_011521582.2 MEF2A [ReferenceRNASequence:11441057] RefSeq:XM_011521586.2 MEF2A [ReferenceRNASequence:11441066] RefSeq:XM_017022190.1 MEF2A [ReferenceRNASequence:11441069] RefSeq:XM_017022191.1 MEF2A [ReferenceRNASequence:11441083] RefSeq:XM_017022193.1 MEF2A [ReferenceRNASequence:11441096] RefSeq:XM_017022194.1 MEF2A
schemaClass	ReferenceGeneProduct
secondaryIdentifier	MEF2A_HUMAN B4DFQ7 F6XG23 O43814 Q14223 Q14224 Q59GX4 Q7Z6C9 Q96D14
sequenceLength	507
species	[Species:48887] Homo sapiens
url	https://purl.uniprot.org/uniprot/Q02078

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-448834] p-T312,T319-MEF2A [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-199909] p-S408-MEF2A [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-199903] MEF2A [nucleoplasm]
(referenceSequence)	[ModifiedResidue:448845] O-phospho-L-threonine at 312 [ModifiedResidue:448821] O-phospho-L-threonine at 319 [ModifiedResidue:199931] O-phospho-L-serine at 408
(interactor)	[UndirectedInteraction:12265363] UniProt:P56524 <-> UniProt:Q02078 (IntAct) [UndirectedInteraction:12212077] UniProt:P05412 <-> UniProt:Q02078 (IntAct)