Q06413 (MEF2C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Myocyte-specific enhancer factor 2C

Gene names

Name:

MEF2C

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	473 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. 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. May also be involved in neurogenesis and in the development of cortical architecture By similarity. Isoform 3 and isoform 4, which lack the repressor domain, are more active than isoform 1 and isoform 2. Ref.6 Ref.7 Ref.12 Ref.13 Ref.15 Ref.17
Subunit structure	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. Interacts with HDAC7 and CARM1 By similarity. Interacts with HDAC4, HDAC7 AND HDAC9; the interaction WITH HDACs represses transcriptional activity. Interacts with MYOCD By similarity. Ref.9 Ref.11 Ref.17
Subcellular location	Nucleus.
Tissue specificity	Expressed in brain and skeletal muscle. Ref.8
Developmental stage	Expression is highest during the early stages of postnatal development, at later stages levels greatly decrease.
Domain	The beta domain, missing in a number of isoforms, is required for enhancement of transcriptional activity By similarity. Ref.15
Post-translational modification	Phosphorylation on Ser-59 enhances DNA binding activity By similarity. Phosphorylation on Ser-396 is required for Lys-391 sumoylation and inhibits transcriptional activity. Ref.14 Ref.16 Ref.18 Acetylated by p300 on several sites in diffentiating myocytes. Acetylation on Lys-4 increases DNA binding and transactivation. Sumoylated on Lys-391 with SUMO2 but not by SUMO1 represses transcriptional activity. Ref.14 Ref.16 Ref.18 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. Ref.6 Ref.7 Ref.10 Ref.13
Involvement in disease	Mental retardation, stereotypic movements, epilepsy and/or cerebral malformations (MRSME) [MIM:613443]: A disorder characterized by severe mental retardation, absent speech, hypotonia, poor eye contact and stereotypic movements. Dysmorphic features include high broad forehead with variable small chin, short nose with anteverted nares, large open mouth, upslanted palpebral fissures and prominent eyebrows. Some patients have seizures. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19
Sequence similarities	Belongs to the MEF2 family. Contains 1 MADS-box domain. Contains 1 Mef2-type DNA-binding domain.

Ontologies

Keywords
Biological process	Apoptosis Differentiation Neurogenesis Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Disease	Mental retardation
Ligand	DNA-binding
Molecular function	Activator Developmental protein
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell homeostasis Inferred from sequence or structural similarity. Source: UniProtKB B cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB B cell receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB MyD88-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome TRIF-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway Traceable author statement. Source: Reactome apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW blood vessel development Inferred from sequence or structural similarity. Source: UniProtKB blood vessel remodeling Inferred from sequence or structural similarity. Source: UniProtKB cardiac ventricle formation Inferred from sequence or structural similarity. Source: UniProtKB cellular response to calcium ion Inferred from sequence or structural similarity. Source: UniProtKB cellular response to drug Inferred from sequence or structural similarity. Source: UniProtKB cellular response to fluid shear stress Inferred from sequence or structural similarity. Source: UniProtKB cellular response to lipopolysaccharide Inferred from sequence or structural similarity. Source: UniProtKB cellular response to parathyroid hormone stimulus Inferred from direct assay PubMed 17696759. Source: UniProtKB cellular response to transforming growth factor beta stimulus Inferred from direct assay PubMed 9770491. Source: UniProtKB cellular response to trichostatin A Inferred from sequence or structural similarity. Source: UniProtKB chondrocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB endochondral ossification Inferred from sequence or structural similarity. Source: UniProtKB epithelial cell proliferation involved in renal tubule morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB germinal center formation Inferred from sequence or structural similarity. Source: UniProtKB glomerulus morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB heart looping Inferred from sequence or structural similarity. Source: UniProtKB humoral immune response Inferred from sequence or structural similarity. Source: UniProtKB innate immune response Traceable author statement. Source: Reactome learning or memory Inferred from sequence or structural similarity. Source: UniProtKB melanocyte differentiation Inferred from sequence or structural similarity PubMed 21610032. Source: UniProtKB muscle cell fate determination Inferred from sequence or structural similarity. Source: UniProtKB myotube differentiation Inferred from expression pattern Ref.2. Source: UniProtKB negative regulation of neuron apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of ossification Inferred from direct assay PubMed 17696759. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 18079734. Source: BHF-UCL nephron tubule epithelial cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome neural crest cell differentiation Inferred from sequence or structural similarity PubMed 21610032. Source: UniProtKB neuron development Inferred from sequence or structural similarity. Source: UniProtKB osteoblast differentiation Inferred from sequence or structural similarity. Source: UniProtKB outflow tract morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB platelet formation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of B cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of alkaline phosphatase activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of behavioral fear response Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of bone mineralization Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cardiac muscle cell differentiation Inferred from direct assay PubMed 9857019. Source: UniProtKB positive regulation of cardiac muscle cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of macrophage apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of myoblast differentiation Inferred from mutant phenotype PubMed 9770491. Source: UniProtKB positive regulation of neuron differentiation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of osteoblast differentiation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein homodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of skeletal muscle cell differentiation Inferred from direct assay PubMed 21556048. Source: UniProtKB positive regulation of skeletal muscle tissue development Inferred from mutant phenotype PubMed 9770491. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from direct assay PubMed 11744164PubMed 11744164PubMed 11744164. Source: UniProtKB primary heart field specification Inferred from sequence or structural similarity. Source: UniProtKB regulation of germinal center formation Inferred from sequence or structural similarity. Source: UniProtKB regulation of megakaryocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB regulation of synaptic activity Inferred from sequence or structural similarity. Source: UniProtKB response to virus Inferred from expression pattern PubMed 21170291. Source: UniProtKB secondary heart field specification Inferred from sequence or structural similarity. Source: UniProtKB sinoatrial valve morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB smooth muscle cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB stress-activated MAPK cascade Traceable author statement. Source: Reactome toll-like receptor 1 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 2 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 3 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 4 signaling pathway Traceable author statement. Source: Reactome ventricular cardiac muscle cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay Ref.2. Source: UniProtKB nuclear speck Inferred from direct assay PubMed 18079734. Source: BHF-UCL nucleus Inferred from direct assay PubMed 11744164PubMed 11744164PubMed 11744164. Source: UniProtKB protein complex Inferred from direct assay PubMed 15486975. Source: UniProtKB
Molecular_function	AT DNA binding Inferred from direct assay PubMed 15486975. Source: UniProtKB DNA binding Inferred from direct assay PubMed 11744164PubMed 11744164. Source: UniProtKB 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 15486975. Source: UniProtKB RNA polymerase II core promoter sequence-specific DNA binding transcription factor activity Inferred from direct assay Ref.2. Source: UniProtKB RNA polymerase II regulatory region sequence-specific DNA binding Inferred from direct assay Ref.2. Source: UniProtKB miRNA binding Inferred from direct assay PubMed 21170291. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q06413-1)

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: Q06413-2)

Also known as: Muscle;

The sequence of this isoform differs from the canonical sequence as follows:
     271-278: Missing.

Isoform 3 (identifier: Q06413-3)

Also known as: hMEF2C-delta32; Brain;

The sequence of this isoform differs from the canonical sequence as follows:
     368-399: Missing.

Isoform 4 (identifier: Q06413-4)

The sequence of this isoform differs from the canonical sequence as follows:
     87-134: Missing.
     271-278: Missing.

Isoform 5 (identifier: Q06413-5)

The sequence of this isoform differs from the canonical sequence as follows:
     107-134: VGHSPESEDKYRKINEDIDLMISRQRLC → ALNKKENKGCESPDPDSSYALTPRTEEKYKKINEEFDNMIKSHKIP
     271-278: Missing.

Note: No experimental confirmation available.

Isoform 6 (identifier: Q06413-6)

The sequence of this isoform differs from the canonical sequence as follows:
     87-134: TLRKKGLNGC...DLMISRQRLC → ALNKKENKGC...DNMIKSHKIP
     271-278: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 473	473	Myocyte-specific enhancer factor 2C		PRO_0000199433
Regions
	Domain	3 – 57	55	MADS-box
	DNA binding	58 – 86	29	Mef2-type Potential
	Region	271 – 278	8	Beta domain
	Region	368 – 399	32	Transcription repressor
	Compositional bias	4 – 31	28	Lys-rich (basic)
	Compositional bias	146 – 183	38	Ser-rich
Sites
	Site	432 – 433	2	Cleavage Probable
Amino acid modifications
	Modified residue	4	1	N6-acetyllysine
	Modified residue	59	1	Phosphoserine; by CK2 By similarity
	Modified residue	116	1	N6-acetyllysine Ref.17
	Modified residue	119	1	N6-acetyllysine Ref.17
	Modified residue	234	1	N6-acetyllysine Ref.17
	Modified residue	239	1	N6-acetyllysine Ref.17
	Modified residue	252	1	N6-acetyllysine Ref.17
	Modified residue	264	1	N6-acetyllysine Ref.17
	Modified residue	293	1	Phosphothreonine; by MAPK14 Ref.6 Ref.7
	Modified residue	300	1	Phosphothreonine; by MAPK14 Ref.6 Ref.7
	Modified residue	396	1	Phosphoserine; by CDK5 Ref.13
	Modified residue	419	1	Phosphoserine; by MAPK7 Ref.6 Ref.7
	Cross-link	391		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.16 Ref.18
Natural variations
	Alternative sequence	87 – 134	48	Missing in isoform 4.		VSP_043339
	Alternative sequence	87 – 134	48	TLRKK…RQRLC → ALNKKENKGCESPDPDSSYA LTPRTEEKYKKINEEFDNMI KSHKIP in isoform 6.		VSP_046251
	Alternative sequence	107 – 134	28	VGHSP…RQRLC → ALNKKENKGCESPDPDSSYA LTPRTEEKYKKINEEFDNMI KSHKIP in isoform 5.		VSP_045478
	Alternative sequence	271 – 278	8	Missing in isoform 2, isoform 4, isoform 5 and isoform 6.		VSP_006248
	Alternative sequence	368 – 399	32	Missing in isoform 3.		VSP_006249
Experimental info
	Mutagenesis	116	1	K → R: Reduced acetylation. Further reduction in acetylation; when associated with R-119. Complete loss of acetylation, 15% less transactivation activity and slightly reduced DNA binding; when associated with R-119; R-234; R-239; R-252 and R-262. Ref.17
	Mutagenesis	119	1	K → R: Reduced acetylation. Further reduction in acetylation; when associated with R-119. Complete loss of acetylation, 15% less transactivation activity and slightly reduced DNA binding; when associated with R-116; R-234; R-239; R-252 and R-262. Ref.17
	Mutagenesis	234	1	K → R: Reduced acetylation. Complete loss of acetylation, 15% less transactivation activity and slightly reduced DNA binding; when associated with R-116; R-119; R-239; R-252 and R-264. Ref.17
	Mutagenesis	239	1	K → R: Reduced acetylation. Complete loss of acetylation, 15% less transactivation activity and slightly reduced DNA binding; when associated with R-116; R-119; R-234; R-252 and R-264. Ref.17
	Mutagenesis	252	1	K → R: Reduced acetylation. Complete loss of acetylation, 15% less transactivation activity and slightly reduced DNA binding; when associated with R-116; R-119; R-234; R-239 and R-264. Ref.17
	Mutagenesis	264	1	K → R: Reduced acetylation. Complete loss of acetylation, 15% less transactivation activity and slightly reduced DNA binding; when associated with R-116; R-119; R-234; R-239 and R-252. Ref.17
	Mutagenesis	271	1	S → A: No effect on transcriptional activation. Ref.15
	Mutagenesis	272	1	E → Q: Reduced transcriptional activation. Completely abolishes transcriptional activation; when associated with N-273 and N-275. Ref.15
	Mutagenesis	273	1	D → N: Reduced transcriptional activation. Completely abolishes transcriptional activation; when associated with Q-272 and N-275. Ref.15
	Mutagenesis	275	1	D → N: Reduced transcriptional activation. Completely abolishes transcriptional activation; when associated with Q-272 and N-273. Ref.15
	Mutagenesis	293	1	T → A: Abolishes MAPK14-mediated phosphorylation. No effect on MAPK7-mediated phosphorylation; when associated with A-300. Ref.6 Ref.7
	Mutagenesis	300	1	T → A: Abolishes MAPK14-mediated phosphorylation. No effect on MAPK7-mediated phosphorylation; when associated with A-293. Ref.6 Ref.7
	Mutagenesis	387	1	S → A: No change in transactivational activation for isoforms with or without the beta domain. Ref.15
	Mutagenesis	391	1	K → R: Abolishes sumoylation. Ref.18
	Mutagenesis	396	1	S → A or C: Abolishes sumoylation. Enhanced transcriptional activity. Ref.13 Ref.15 Ref.18
	Mutagenesis	396	1	S → A: No change in transactivational activation for isoforms with or without the beta domain. Ref.13 Ref.15 Ref.18
	Mutagenesis	396	1	S → E: No effect on sumoylation. No effect on transcriptional activity. Ref.13 Ref.15 Ref.18
	Mutagenesis	419	1	S → A: No effect on MAPK14-mediated phosphorylation. Abolishes MAPK7-mediated phosphorylation and reduces transactivation activity. Ref.6 Ref.7
	Mutagenesis	432	1	D → A: Abolishes cleavage by caspase 7. Ref.12
	Sequence conflict	390	1	I → T in AL833268. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: A7982020BB8C8949	FASTA	473	51,221
	10 20 30 40 50 60 MGRKKIQITR IMDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNS TNKLFQYAST 70 80 90 100 110 120 DMDKVLLKYT EYNEPHESRT NSDIVETLRK KGLNGCDSPD PDADDSVGHS PESEDKYRKI 130 140 150 160 170 180 NEDIDLMISR QRLCAVPPPN FEMPVSIPVS SHNSLVYSNP VSSLGNPNLL PLAHPSLQRN 190 200 210 220 230 240 SMSPGVTHRP PSAGNTGGLM GGDLTSGAGT SAGNGYGNPR NSPGLLVSPG NLNKNMQAKS 250 260 270 280 290 300 PPPMNLGMNN RKPDLRVLIP PGSKNTMPSV SEDVDLLLNQ RINNSQSAQS LATPVVSVAT 310 320 330 340 350 360 PTLPGQGMGG YPSAISTTYG TEYSLSSADL SSLSGFNTAS ALHLGSVTGW QQQHLHNMPP 370 380 390 400 410 420 SALSQLGACT STHLSQSSNL SLPSTQSLNI KSEPVSPPRD RTTTPSRYPQ HTRHEAGRSP 430 440 450 460 470 VDSLSSCSSS YDGSDREDHR NEFHSPIGLT RPSPDERESP SVKRMRLSEG WAT
	Isoform 2 (Muscle) [UniParc]. Checksum: A2059C6AACB2F07B	FASTA	465	50,336
	10 20 30 40 50 60 MGRKKIQITR IMDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNS TNKLFQYAST 70 80 90 100 110 120 DMDKVLLKYT EYNEPHESRT NSDIVETLRK KGLNGCDSPD PDADDSVGHS PESEDKYRKI 130 140 150 160 170 180 NEDIDLMISR QRLCAVPPPN FEMPVSIPVS SHNSLVYSNP VSSLGNPNLL PLAHPSLQRN 190 200 210 220 230 240 SMSPGVTHRP PSAGNTGGLM GGDLTSGAGT SAGNGYGNPR NSPGLLVSPG NLNKNMQAKS 250 260 270 280 290 300 PPPMNLGMNN RKPDLRVLIP PGSKNTMPSV NQRINNSQSA QSLATPVVSV ATPTLPGQGM 310 320 330 340 350 360 GGYPSAISTT YGTEYSLSSA DLSSLSGFNT ASALHLGSVT GWQQQHLHNM PPSALSQLGA 370 380 390 400 410 420 CTSTHLSQSS NLSLPSTQSL NIKSEPVSPP RDRTTTPSRY PQHTRHEAGR SPVDSLSSCS 430 440 450 460 SSYDGSDRED HRNEFHSPIG LTRPSPDERE SPSVKRMRLS EGWAT
	Isoform 3 (hMEF2C-delta32) (Brain) [UniParc]. Checksum: BF94FD79A54FEEB1	FASTA	441	47,872
	10 20 30 40 50 60 MGRKKIQITR IMDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNS TNKLFQYAST 70 80 90 100 110 120 DMDKVLLKYT EYNEPHESRT NSDIVETLRK KGLNGCDSPD PDADDSVGHS PESEDKYRKI 130 140 150 160 170 180 NEDIDLMISR QRLCAVPPPN FEMPVSIPVS SHNSLVYSNP VSSLGNPNLL PLAHPSLQRN 190 200 210 220 230 240 SMSPGVTHRP PSAGNTGGLM GGDLTSGAGT SAGNGYGNPR NSPGLLVSPG NLNKNMQAKS 250 260 270 280 290 300 PPPMNLGMNN RKPDLRVLIP PGSKNTMPSV SEDVDLLLNQ RINNSQSAQS LATPVVSVAT 310 320 330 340 350 360 PTLPGQGMGG YPSAISTTYG TEYSLSSADL SSLSGFNTAS ALHLGSVTGW QQQHLHNMPP 370 380 390 400 410 420 SALSQLGDRT TTPSRYPQHT RHEAGRSPVD SLSSCSSSYD GSDREDHRNE FHSPIGLTRP 430 440 SPDERESPSV KRMRLSEGWA T
	Isoform 4 [UniParc]. Checksum: 35B8B495FAB6FA3C	FASTA	417	44,935
	10 20 30 40 50 60 MGRKKIQITR IMDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNS TNKLFQYAST 70 80 90 100 110 120 DMDKVLLKYT EYNEPHESRT NSDIVEAVPP PNFEMPVSIP VSSHNSLVYS NPVSSLGNPN 130 140 150 160 170 180 LLPLAHPSLQ RNSMSPGVTH RPPSAGNTGG LMGGDLTSGA GTSAGNGYGN PRNSPGLLVS 190 200 210 220 230 240 PGNLNKNMQA KSPPPMNLGM NNRKPDLRVL IPPGSKNTMP SVNQRINNSQ SAQSLATPVV 250 260 270 280 290 300 SVATPTLPGQ GMGGYPSAIS TTYGTEYSLS SADLSSLSGF NTASALHLGS VTGWQQQHLH 310 320 330 340 350 360 NMPPSALSQL GACTSTHLSQ SSNLSLPSTQ SLNIKSEPVS PPRDRTTTPS RYPQHTRHEA 370 380 390 400 410 GRSPVDSLSS CSSSYDGSDR EDHRNEFHSP IGLTRPSPDE RESPSVKRMR LSEGWAT
	Isoform 5 [UniParc]. Checksum: 54ECDC4D04211C48	FASTA	483	52,328
	10 20 30 40 50 60 MGRKKIQITR IMDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNS TNKLFQYAST 70 80 90 100 110 120 DMDKVLLKYT EYNEPHESRT NSDIVETLRK KGLNGCDSPD PDADDSALNK KENKGCESPD 130 140 150 160 170 180 PDSSYALTPR TEEKYKKINE EFDNMIKSHK IPAVPPPNFE MPVSIPVSSH NSLVYSNPVS 190 200 210 220 230 240 SLGNPNLLPL AHPSLQRNSM SPGVTHRPPS AGNTGGLMGG DLTSGAGTSA GNGYGNPRNS 250 260 270 280 290 300 PGLLVSPGNL NKNMQAKSPP PMNLGMNNRK PDLRVLIPPG SKNTMPSVNQ RINNSQSAQS 310 320 330 340 350 360 LATPVVSVAT PTLPGQGMGG YPSAISTTYG TEYSLSSADL SSLSGFNTAS ALHLGSVTGW 370 380 390 400 410 420 QQQHLHNMPP SALSQLGACT STHLSQSSNL SLPSTQSLNI KSEPVSPPRD RTTTPSRYPQ 430 440 450 460 470 480 HTRHEAGRSP VDSLSSCSSS YDGSDREDHR NEFHSPIGLT RPSPDERESP SVKRMRLSEG WAT
	Isoform 6 [UniParc]. Checksum: B78282622DC98CE5	FASTA	463	50,242
	10 20 30 40 50 60 MGRKKIQITR IMDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNS TNKLFQYAST 70 80 90 100 110 120 DMDKVLLKYT EYNEPHESRT NSDIVEALNK KENKGCESPD PDSSYALTPR TEEKYKKINE 130 140 150 160 170 180 EFDNMIKSHK IPAVPPPNFE MPVSIPVSSH NSLVYSNPVS SLGNPNLLPL AHPSLQRNSM 190 200 210 220 230 240 SPGVTHRPPS AGNTGGLMGG DLTSGAGTSA GNGYGNPRNS PGLLVSPGNL NKNMQAKSPP 250 260 270 280 290 300 PMNLGMNNRK PDLRVLIPPG SKNTMPSVNQ RINNSQSAQS LATPVVSVAT PTLPGQGMGG 310 320 330 340 350 360 YPSAISTTYG TEYSLSSADL SSLSGFNTAS ALHLGSVTGW QQQHLHNMPP SALSQLGACT 370 380 390 400 410 420 STHLSQSSNL SLPSTQSLNI KSEPVSPPRD RTTTPSRYPQ HTRHEAGRSP VDSLSSCSSS 430 440 450 460 YDGSDREDHR NEFHSPIGLT RPSPDERESP SVKRMRLSEG WAT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"MEF2C, a MADS/MEF2-family transcription factor expressed in a laminar distribution in cerebral cortex." Leifer D., Krainc D., Yu Y.-T., McDermott J., Breitbart R.E., Heng J., Neve R.L., Kosofsky B., Nadal-Ginard B., Lipton S.A. Proc. Natl. Acad. Sci. U.S.A. 90:1546-1550(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3). Tissue: Fetal brain and Muscle.
[2]	"hMEF2C gene encodes skeletal muscle- and brain-specific transcription factors." McDermott J.C., Cardoso M.C., Yu Y.-T., Andres V., Leifer D., Krainc D., Lipton S.A., Nadal-Ginard B. Mol. Cell. Biol. 13:2564-2577(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Skeletal muscle.
[3]	"Identification and characterization of a new splice variant of human MEF2C." Infantino V., Convertini P., Palmieri F., Iacobazzi V. Submitted (MAY-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4). Tissue: Skeletal muscle.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 5 AND 6). Tissue: Skeletal muscle.
[5]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C." Kato Y., Kravchenko V.V., Tapping R.I., Han J., Ulevitch R.J., Lee J.-D. EMBO J. 16:7054-7066(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-293; THR-300 AND SER-419, FUNCTION, MUTAGENESIS OF THR-293; THR-300 AND SER-419.
[7]	"Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation." Han J., Jiang Y., Li Z., Kravchenko V.V., Ulevitch R.J. Nature 386:296-299(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-293; THR-300 AND SER-419, FUNCTION, MUTAGENESIS OF THR-293; THR-300 AND SER-419.
[8]	"Characterization of myocyte enhancer factor 2 (MEF2) expression in B and T cells: MEF2C is a B cell-restricted transcription factor in lymphocytes." Swanson B.J., Jaeck H.-M., Lyons G.E. Mol. Immunol. 35:445-458(1998) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor." Wang A.H., Bertos N.R., Vezmar M., Pelletier N., Crosato M., Heng H.H., Th'ng J., Han J., Yang X.-J. Mol. Cell. Biol. 19:7816-7827(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HDAC4.
[10]	"Big mitogen-activated kinase regulates multiple members of the MEF2 protein family." Kato Y., Zhao M., Morikawa A., Sugiyama T., Chakravortty D., Koide N., Yoshida T., Tapping R.I., Yang Y., Yokochi T., Lee J.D. J. Biol. Chem. 275:18534-18540(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY MAPK7.
[11]	"Cloning and characterization of a histone deacetylase, HDAC9." Zhou X., Marks P.A., Rifkind R.A., Richon V.M. Proc. Natl. Acad. Sci. U.S.A. 98:10572-10577(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HDAC9.
[12]	"Dominant-interfering forms of MEF2 generated by caspase cleavage contribute to NMDA-induced neuronal apoptosis." Okamoto S., Li Z., Ju C., Scholzke M.N., Mathews E., Cui J., Salvesen G.S., Bossy-Wetzel E., Lipton S.A. Proc. Natl. Acad. Sci. U.S.A. 99:3974-3979(2002) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING AT ASP-432, FUNCTION, MUTAGENESIS OF ASP-432.
[13]	"Phosphorylation and alternative pre-mRNA splicing converge to regulate myocyte enhancer factor 2C activity." Zhu B., Gulick T. Mol. Cell. Biol. 24:8264-8275(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-396, MASS SPECTROMETRY, MUTAGENESIS OF SER-396, FUNCTION OF ISOFORMS.
[14]	"Systematic identification and analysis of mammalian small ubiquitin-like modifier substrates." Gocke C.B., Yu H., Kang J. J. Biol. Chem. 280:5004-5012(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION.
[15]	"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: FUNCTION OF BETA DOMAIN, MUTAGENESIS OF SER-271; GLU-272; ASP-273; ASP-275; SER-387 AND SER-396.
[16]	"Association with class IIa histone deacetylases upregulates the sumoylation of MEF2 transcription factors." Gregoire S., Yang X.-J. Mol. Cell. Biol. 25:2273-2287(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-391.
[17]	"Myocyte enhancer factor 2 acetylation by p300 enhances its DNA binding activity, transcriptional activity, and myogenic differentiation." Ma K., Chan J.K., Zhu G., Wu Z. Mol. Cell. Biol. 25:3575-3582(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION AT LYS-116; LYS-119; LYS-234; LYS-239; LYS-252 AND LYS-264, INTERACTION WITH EP300, FUNCTION, DNA-BINDING, MUTAGENESIS OF LYS-116; LYS-119; LYS-234; LYS-239; LYS-252 AND LYS-264.
[18]	"Phosphorylation-facilitated sumoylation of MEF2C negatively regulates its transcriptional activity." Kang J., Gocke C.B., Yu H. BMC Biochem. 7:5-5(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-391, MUTAGENESIS OF LYS-391 AND SER-396.
[19]	"MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations." Le Meur N., Holder-Espinasse M., Jaillard S., Goldenberg A., Joriot S., Amati-Bonneau P., Guichet A., Barth M., Charollais A., Journel H., Auvin S., Boucher C., Kerckaert J.P., David V., Manouvrier-Hanu S., Saugier-Veber P., Frebourg T., Dubourg C., Andrieux J., Bonneau D. J. Med. Genet. 47:22-29(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN MRSME.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L08895 mRNA. Translation: AAA59578.1. S57212 mRNA. Translation: AAB25838.1. FM163484 mRNA. Translation: CAQ57795.2. AL833268 mRNA. No translation available. AL833274 mRNA. No translation available. AC008525 Genomic DNA. No translation available. AC008835 Genomic DNA. No translation available.
IPI	IPI00215666. IPI00289092. IPI00909329. IPI00964670. IPI00969463. IPI01015483.
PIR	A47284.
RefSeq	NP_001124477.1. NM_001131005.2. NP_001180276.1. NM_001193347.1. NP_001180277.1. NM_001193348.1. NP_001180278.1. NM_001193349.1. NP_001180279.1. NM_001193350.1. NP_002388.2. NM_002397.4.
UniGene	Hs.649965.
3D structure databases
ProteinModelPortal	Q06413.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q06413. 9 interactions.
MINT	MINT-125556.
STRING	9606.ENSP00000396219.
PTM databases
PhosphoSite	Q06413.
Polymorphism databases
DMDM	2500875.
Proteomic databases
PaxDb	Q06413.
PRIDE	Q06413.
Protocols and materials databases
DNASU	4208.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000340208; ENSP00000340874; ENSG00000081189. ENST00000424173; ENSP00000389610; ENSG00000081189. ENST00000437473; ENSP00000396219; ENSG00000081189. ENST00000510942; ENSP00000422390; ENSG00000081189. ENST00000514015; ENSP00000424606; ENSG00000081189. ENST00000514028; ENSP00000426665; ENSG00000081189. ENST00000539796; ENSP00000441153; ENSG00000081189.
GeneID	4208.
KEGG	hsa:4208.
UCSC	uc003kji.2. human. uc003kjj.3. human.
Organism-specific databases
CTD	4208.
GeneCards	GC05M088051.
HGNC	HGNC:6996. MEF2C.
HPA	HPA005533.
MIM	600662. gene. 613443. phenotype.
neXtProt	NX_Q06413.
Orphanet	228384. 5q14.3 microdeletion syndrome.
PharmGKB	PA30734.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5068.
HOGENOM	HOG000230620.
HOVERGEN	HBG053944.
InParanoid	Q06413.
KO	K04454.
OrthoDB	EOG4DFPNH.
Enzyme and pathway databases
Pathway_Interaction_DB	smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling. hdac_classii_pathway. Signaling events mediated by HDAC Class II. p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta. mapktrkpathway. Trk receptor signaling mediated by the MAPK pathway.
Reactome	REACT_111045. Developmental Biology. REACT_111102. Signal Transduction. REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q06413.
Bgee	Q06413.
CleanEx	HS_MEF2C.
Genevestigator	Q06413.
GermOnline	ENSG00000081189. Homo sapiens.
Family and domain databases
InterPro	IPR022102. HJURP_C. IPR002100. TF_MADSbox. [Graphical view]
Pfam	PF12347. HJURP_C. 1 hit. PF00319. SRF-TF. 1 hit. [Graphical view]
PRINTS	PR00404. MADSDOMAIN.
SMART	SM00432. MADS. 1 hit. [Graphical view]
SUPFAM	SSF55455. TF_MADSbox. 1 hit.
PROSITE	PS00350. MADS_BOX_1. 1 hit. PS50066. MADS_BOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MEF2C. human.
GenomeRNAi	4208.
NextBio	16578.
SOURCE	Search...

Entry information

Entry name

MEF2C_HUMAN

Accession

Primary (citable) accession number: Q06413
Secondary accession number(s): C9JMZ0, D7F7N5, F8W7V7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.