Reactome | UniProt:Q8CFN5 Mef2c

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UniProt:Q8CFN5 Mef2c Show undefined attributes

chain	chain:1-474
checksum	CEFC2DB21E89632A
comment	FUNCTION Transcription activator which binds specifically to the MEF2 element present in the regulatory regions of many muscle-specific genes. Controls cardiac morphogenesis and myogenesis, and is also involved in vascular development (PubMed:33941892). Enhances transcriptional activation mediated by SOX18 (PubMed:11554755). May also be involved in neurogenesis and in the development of cortical architecture. Isoforms that lack the repressor domain are more active than isoform 1 (By similarity). Plays an essential role in hippocampal-dependent learning and memory by suppressing the number of excitatory synapses and thus regulating basal and evoked synaptic transmission. Crucial for normal neuronal development, distribution, and electrical activity in the neocortex. Necessary for proper development of megakaryocytes and platelets and for bone marrow B-lymphopoiesis. Required for B-cell survival and proliferation in response to BCR stimulation, efficient IgG1 antibody responses to T-cell-dependent antigens and for normal induction of germinal center B-cells.SUBUNIT Forms a complex with class II HDACs in undifferentiating cells. On myogenic differentiation, HDACs are released into the cytoplasm allowing MEF2s to interact with other proteins for activation. Interacts with EP300 in differentiating cells; the interaction acetylates MEF2C leading to increased DNA binding and activation (By similarity). Interacts with HDAC7 and CARM1 (PubMed:11279209, PubMed:11713257). Interacts with HDAC4, HDAC7 AND HDAC9; the interaction with HDACs represses transcriptional activity (By similarity). Interacts with LPIN1 (PubMed:19753306). Interacts with MYOCD (PubMed:16818234). Interacts with AKAP13 (PubMed:20139090). Interacts with FOXK1; the interaction inhibits MEF2C transactivation activity (PubMed:22956541). Interacts (via N-terminus) with HABP4; this interaction decreases DNA-binding activity of MEF2C in myocardial cells in response to mechanical stress (By similarity). Interacts with JPH2; interaction specifically takes place with the Junctophilin-2 N-terminal fragment cleavage product of JPH2 (PubMed:30409805). Interacts (via MADS box) with SOX18 (PubMed:11554755). Interacts with PHF7; the interaction promotes MEF2C binding to its transcription targets (PubMed:33941892).INTERACTION Additional isoforms seem to exist.TISSUE SPECIFICITY Widely expressed though mainly restricted to skeletal and cardiac muscle, brain, neurons and lymphocytes. Beta domain-lacking isoforms are the most predominantly expressed in all tissues including skeletal and cardiac muscle and brain. Only brain expresses all isoforms. Expression occurs primarily in the internal granule cell layer of the olfactory bulb, cortex, thalamus, hippocampus and cerebellum. Low levels in the cerebellum and hindbrain. Expressed throughout the cortex, including the frontal and entorhinal cortex, dentate gyrus, and basolateral amygdala. Selectively expressed in B-cells but not in T-cells, and its expression increases as B-cells mature.DEVELOPMENTAL STAGE Expressed in developing endothelial cells and smooth muscle cells, as well as in surrounding mesenchyme, during embryogenesis. Up-regulated during myogenesis.DOMAIN The beta domain, missing in a number of isoforms, is required for enhancement of transcriptional activity.PTM Phosphorylation on Ser-59 enhances DNA binding activity (By similarity). Phosphorylation on Ser-396 is required for Lys-391 sumoylation and inhibits transcriptional activity.PTM Acetylated by p300 on several sites in diffentiating myocytes (By similarity). Acetylation on Lys-4 increases DNA binding and transactivation.PTM Sumoylated on Lys-391 with SUMO2 but not by SUMO1 represses transcriptional activity.PTM Proteolytically cleaved in cerebellar granule neurons, probably by caspase 7, following neurotoxicity. Preferentially cleaves the CDK5-mediated hyperphosphorylated form which leads to neuron apoptosis and transcriptional inactivation (By similarity).DISRUPTION PHENOTYPE Mice show impairment in hippocampal-dependent learning and also increase in the number of excitatory synapses and potentiation of basal and evoked synaptic transmission. Mice surviving to adulthood manifest smaller, apparently less mature neurons and smaller whole brain size, with resultant aberrant electrophysiology and behavior. Mice exhibit thrombocytopenia and a defect in B-lymphopoiesis.SIMILARITY Belongs to the MEF2 family.
created	[InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53
crossReference	[DatabaseIdentifier:12461268] RefSeq:XP_036013783.1 [DatabaseIdentifier:12461253] RefSeq:XP_030103037.1 [DatabaseIdentifier:12461263] RefSeq:NP_001334495.1 [DatabaseIdentifier:12461259] RefSeq:NP_001334498.1 [DatabaseIdentifier:12461279] RefSeq:XP_011242794.1 [DatabaseIdentifier:12461254] RefSeq:XP_030103036.1 [DatabaseIdentifier:12461266] RefSeq:XP_006517186.1 [DatabaseIdentifier:12461272] RefSeq:NP_001334502.1 [DatabaseIdentifier:12461257] RefSeq:XP_030103032.1 [DatabaseIdentifier:12461269] RefSeq:NP_001334500.1 [DatabaseIdentifier:12461271] RefSeq:NP_001164008.1 [DatabaseIdentifier:12461252] RefSeq:XP_006517195.1 [DatabaseIdentifier:12461273] RefSeq:NP_001334503.1 [DatabaseIdentifier:11516449] ENSEMBL:ENSMUSG00000005583 [DatabaseIdentifier:11633506] ENSEMBL:ENSMUSP00000143420 [DatabaseIdentifier:11633507] ENSEMBL:ENSMUSP00000138826 [DatabaseIdentifier:11633512] ENSEMBL:ENSMUSP00000143227 [DatabaseIdentifier:11633508] ENSEMBL:ENSMUSP00000143212 [DatabaseIdentifier:11633510] ENSEMBL:ENSMUSP00000143401 [DatabaseIdentifier:11633509] ENSEMBL:ENSMUSP00000143742 [DatabaseIdentifier:11633511] ENSEMBL:ENSMUSP00000143315 [DatabaseIdentifier:11756209] ENSEMBL:ENSMUST00000197681 [DatabaseIdentifier:11756211] ENSEMBL:ENSMUST00000198199 [DatabaseIdentifier:11756210] ENSEMBL:ENSMUST00000185052 [DatabaseIdentifier:11756205] ENSEMBL:ENSMUST00000197146 [DatabaseIdentifier:11756208] ENSEMBL:ENSMUST00000199450 [DatabaseIdentifier:11756207] ENSEMBL:ENSMUST00000199019 [DatabaseIdentifier:11756206] ENSEMBL:ENSMUST00000199105 [DatabaseIdentifier:11804740] GlyGen:Q8CFN5 [DatabaseIdentifier:11937153] MGI:99458 [DatabaseIdentifier:12188775] PDB:5F28 [DatabaseIdentifier:12267279] PRO:Q8CFN5 [DatabaseIdentifier:12461261] RefSeq:NP_001334497.1 [DatabaseIdentifier:12461264] RefSeq:XP_036013780.1 [DatabaseIdentifier:12461275] RefSeq:NP_001334505.1 [DatabaseIdentifier:12461258] RefSeq:XP_006517189.1 [DatabaseIdentifier:12461270] RefSeq:NP_001334501.1 [DatabaseIdentifier:12461267] RefSeq:XP_006517187.1 [DatabaseIdentifier:12461265] RefSeq:NP_001334493.1 [DatabaseIdentifier:12461278] RefSeq:NP_001334506.1 [DatabaseIdentifier:12461260] RefSeq:XP_036013779.1 [DatabaseIdentifier:12461262] RefSeq:NP_001334496.1 [DatabaseIdentifier:12461255] RefSeq:NP_079558.1 [DatabaseIdentifier:12461256] RefSeq:XP_030103035.1 [DatabaseIdentifier:12461277] RefSeq:XP_006517190.1 [DatabaseIdentifier:12461274] RefSeq:XP_017170894.1 [DatabaseIdentifier:12461276] RefSeq:NP_001334504.1
databaseName	UniProt
dbId	237109
description	recommendedName: fullName evidence="31"Myocyte-specific enhancer factor 2C alternativeName: fullName evidence="32"Myocyte enhancer factor 2C
displayName	UniProt:Q8CFN5 Mef2c
geneName	Mef2c
identifier	Q8CFN5
isSequenceChanged	false
keyword	3D-structure Acetylation Activator Alternative splicing Apoptosis Cytoplasm Developmental protein Differentiation DNA-binding Isopeptide bond Neurogenesis Nucleus Phosphoprotein Reference proteome Transcription Transcription regulation Ubl conjugation
modified	[InstanceEdit:9948485] Weiser, Joel, 2025-05-21
moleculeType	Protein
name	Mef2c
otherIdentifier	10406434 104590_at 104591_g_at 104592_i_at 109748_at 114712_at 1421027_a_at 1421028_a_at 1424852_at 1451506_at 1451507_at 163739_at 17260 17288917 4314429 4333244 4345389 4359487 4362681 4396166 4411148 4428837 4538745 4603235 4698686 4761525 4767959 4783026 4797984 4818416 4827019 4827250 4827389 4913196 4919069 4962866 4976592 4977512 5008582 5094965 5103668 5123835 5129757 5130923 5160588 5177570 5177935 5251369 5364902 5393896 5412458 5453745 5531043 5568234 5604938 5607430 97357_at A_51_P135802 A_52_P282110 A_55_P2155620 A_55_P2730921 A_65_P01126 A_65_P11889 GE40655 GO:0000122 GO:0000165 GO:0000976 GO:0000977 GO:0000978 GO:0000981 GO:0000987 GO:0001228 GO:0001568 GO:0001649 GO:0001764 GO:0001782 GO:0001947 GO:0001958 GO:0001974 GO:0002062 GO:0002376 GO:0002467 GO:0002634 GO:0002931 GO:0003012 GO:0003138 GO:0003139 GO:0003151 GO:0003185 GO:0003211 GO:0003677 GO:0003680 GO:0003682 GO:0003700 GO:0005515 GO:0005634 GO:0005654 GO:0005737 GO:0005829 GO:0006355 GO:0006915 GO:0006959 GO:0007399 GO:0007411 GO:0007507 GO:0007519 GO:0007521 GO:0007611 GO:0010467 GO:0010628 GO:0010629 GO:0014033 GO:0014898 GO:0014902 GO:0016528 GO:0016607 GO:0019899 GO:0030154 GO:0030182 GO:0030220 GO:0030224 GO:0030279 GO:0030318 GO:0030501 GO:0030890 GO:0032991 GO:0035050 GO:0035914 GO:0035984 GO:0042100 GO:0042826 GO:0043410 GO:0043523 GO:0043524 GO:0043537 GO:0043565 GO:0045165 GO:0045652 GO:0045663 GO:0045666 GO:0045669 GO:0045893 GO:0045944 GO:0046928 GO:0046982 GO:0046983 GO:0048167 GO:0048643 GO:0048666 GO:0048667 GO:0048703 GO:0048704 GO:0048856 GO:0048870 GO:0050680 GO:0050853 GO:0050877 GO:0051145 GO:0051963 GO:0051966 GO:0055007 GO:0055012 GO:0060021 GO:0060025 GO:0060045 GO:0060079 GO:0060297 GO:0060536 GO:0060998 GO:0061333 GO:0061629 GO:0071222 GO:0071277 GO:0071374 GO:0071466 GO:0071498 GO:0071560 GO:0071837 GO:0071838 GO:0071864 GO:0072102 GO:0072160 GO:0097492 GO:0098794 GO:0098989 GO:0098990 GO:0140297 GO:1902287 GO:1904706 GO:1904753 GO:1905563 GO:1990837 GO:2000111 GO:2000727 GO:2000987 GO:2001013 GO:2001016 ILMN_1214950 ILMN_1220270 ILMN_2520812 ILMN_2732465 ILMN_2887992 Msa.939.0_at aa183623_s_at mMC020985 mMC023879
physicalEntity	[EntityWithAccessionedSequence:R-MMU-199938] Mef2c [nucleoplasm] - Mus musculus [EntityWithAccessionedSequence:R-MMU-1605569] Mef2c [nucleoplasm] - Mus musculus [EntityWithAccessionedSequence:R-MMU-448838] phospho-Mef2c [nucleoplasm] - Mus musculus
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:11380512] BioGPS Gene:17260 Mef2c [ReferenceDNASequence:12712844] UCSC:Q8CFN5 Mef2c [ReferenceDNASequence:11917505] KEGG:mmu:17260 Mef2c [ReferenceDNASequence:12010301] Monarch:17260 Mef2c [ReferenceDNASequence:12094394] NCBI Gene:17260 Mef2c
referenceTranscript	[ReferenceRNASequence:12642776] RefSeq:XM_036157886.1 Mef2c [ReferenceRNASequence:12642772] RefSeq:NM_001347564.2 Mef2c [ReferenceRNASequence:12642777] RefSeq:NM_001170537.2 Mef2c [ReferenceRNASequence:12642770] RefSeq:XM_006517127.5 Mef2c [ReferenceRNASequence:12642780] RefSeq:XM_011244492.4 Mef2c [ReferenceRNASequence:12642763] RefSeq:NM_001347569.2 Mef2c [ReferenceRNASequence:12642765] RefSeq:NM_001347568.2 Mef2c [ReferenceRNASequence:12642787] RefSeq:NM_001347573.2 Mef2c [ReferenceRNASequence:12642774] RefSeq:XM_006517124.5 Mef2c [ReferenceRNASequence:12642762] RefSeq:XM_036157887.1 Mef2c [ReferenceRNASequence:12642764] RefSeq:XM_006517126.4 Mef2c [ReferenceRNASequence:12642779] RefSeq:NM_001347571.2 Mef2c [ReferenceRNASequence:12642789] RefSeq:XM_036157890.1 Mef2c [ReferenceRNASequence:12642783] RefSeq:NM_001347576.2 Mef2c [ReferenceRNASequence:12642781] RefSeq:XM_030247172.2 Mef2c [ReferenceRNASequence:12642768] RefSeq:XM_030247176.2 Mef2c [ReferenceRNASequence:12642769] RefSeq:NM_001347566.2 Mef2c [ReferenceRNASequence:12642784] RefSeq:NM_001347575.2 Mef2c [ReferenceRNASequence:12642785] RefSeq:XM_006517132.5 Mef2c [ReferenceRNASequence:12642775] RefSeq:XM_017315405.3 Mef2c [ReferenceRNASequence:12642771] RefSeq:XM_030247177.2 Mef2c [ReferenceRNASequence:12642788] RefSeq:NM_025282.4 Mef2c [ReferenceRNASequence:12642778] RefSeq:NM_001347572.2 Mef2c [ReferenceRNASequence:12642786] RefSeq:NM_001347574.2 Mef2c [ReferenceRNASequence:12642773] RefSeq:XM_006517123.4 Mef2c [ReferenceRNASequence:12642766] RefSeq:XM_030247175.2 Mef2c [ReferenceRNASequence:12642782] RefSeq:NM_001347577.2 Mef2c [ReferenceRNASequence:12642767] RefSeq:NM_001347567.2 Mef2c
schemaClass	ReferenceGeneProduct
secondaryIdentifier	MEF2C_MOUSE Q8R0H1 Q9D7L0 Q9QW20
sequenceLength	474
species	[Species:48892] Mus musculus
stId	uniprot:Q8CFN5
url	http://purl.uniprot.org/uniprot/Q8CFN5

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-MMU-199938] Mef2c [nucleoplasm] [EntityWithAccessionedSequence:R-MMU-1605569] Mef2c [nucleoplasm] [EntityWithAccessionedSequence:R-MMU-448838] phospho-Mef2c [nucleoplasm]
(referenceSequence)	[ModifiedResidue:10018328] O-phospho-L-threonine at 300 (in Homo sapiens) [ModifiedResidue:10018329] O-phospho-L-serine at 387 (in Homo sapiens) [ModifiedResidue:10018327] O-phospho-L-threonine at 293 (in Homo sapiens)
(interactor)	[UndirectedInteraction:11283711] UniProt:Q8CFN5 <-> UniProt:Q9QZR5 (IntAct) [UndirectedInteraction:11283713] UniProt:Q8CFN5 <-> UniProt:Q8WUI4 (IntAct)

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