Reviewed, UniProtKB/Swiss-Prot Q06413 (MEF2C_HUMAN)

Names and origin

Protein names

Recommended name:
    Myocyte-specific enhancer factor 2C

Gene names

Name:

MEF2C

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	473 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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. 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.
Subunit structure	Interacts with HDAC7 and CARM1 By similarity. Interacts with HDAC4 and HDAC9.
Subcellular location	Nucleus.
Tissue specificity	Expressed in brain and skeletal muscle.
Developmental stage	Expression is highest during the early stages of postnatal development, at later stages levels greatly decrease.
Post-translational modification	Phosphorylated on Ser-59; which enhances DNA binding activity By similarity. Phosphorylated on Ser-396; which is required for Lys-391 sumoylation and inhibits transcriptional activity. Sumoylated on Ser-396 by SUMO2 but not SUMO1; which represses transcriptional activity.
Sequence similarities	Belongs to the MEF2 family. Contains 1 MADS-box domain. Contains 1 Mef2-type DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	muscle development Ref.2 Traceable author statement. Source: ProtInc nervous system development Ref.2 Traceable author statement. Source: ProtInc
Cellular component	nucleus Inferred from electronic annotation. Source: InterPro
Molecular function	RNA polymerase II transcription factor activity Ref.2 Traceable author statement. Source: ProtInc sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro transcription factor activity Non-traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Notes: 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.

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	368 – 399	32	Transcription repressor
	Compositional bias	4 – 31	28	Lys-rich (basic)
	Compositional bias	146 – 183	38	Ser-rich
Amino acid modifications
	Modified residue	59	1	Phosphoserine; by CK2 By similarity
	Modified residue	396	1	Phosphoserine
	Cross-link	391		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Natural variations
	Alternative sequence	271 – 278	8	Missing in isoform 2.		VSP_006248
	Alternative sequence	368 – 399	32	Missing in isoform 3.		VSP_006249
Experimental info
	Mutagenesis	391	1	K → R: Abolishes sumoylation
	Mutagenesis	396	1	S → A or C: Abolishes sumoylation. Enhanced transcriptional activity
	Mutagenesis	396	1	S → E: No effect on sumoylation. No effect on transcriptional activity

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		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		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

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: 7679508] [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: 8455629] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Skeletal muscle.
[3]	"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: 10523670] [Abstract] Cited for: INTERACTION WITH HDAC4.
[4]	"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: 11535832] [Abstract] Cited for: INTERACTION WITH HDAC9.
[5]	"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: 15340086] [Abstract] Cited for: PHOSPHORYLATION AT SER-396, MASS SPECTROMETRY, MUTAGENESIS OF SER-396, FUNCTION OF ISOFORMS.
[6]	"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: 15561718] [Abstract] Cited for: SUMOYLATION.
[7]	"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: 15743823] [Abstract] Cited for: SUMOYLATION AT LYS-391.
[8]	"Phosphorylation-facilitated sumoylation of MEF2C negatively regulates its transcriptional activity." Kang J., Gocke C.B., Yu H. BMC Biochem. 7:5-5(2006) [PubMed: 16478538] [Abstract] Cited for: SUMOYLATION AT LYS-391, MUTAGENESIS OF LYS-391 AND SER-396.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	L08895 mRNA. Translation: AAA59578.1. S57212 mRNA. Translation: AAB25838.1.
PIR	A47284.
RefSeq	NP_002388.2.
UniGene	Hs.699175
3D structure databases
HSSP	HSSP built from PDB template 1EGW based on UniProtKB Q02078.
SMR	Q06413. Positions 2-93.
ModBase	Search...
PTM databases
PhosphoSite	Q06413.
Genome annotation databases
Ensembl	ENSG00000081189. Homo sapiens. [Contig view]
GeneID	4208.
KEGG	hsa:4208.
Organism-specific databases
H-InvDB	HIX0005020.
HGNC	HGNC:6996. MEF2C.
HPA	HPA005533.
MIM	600662. gene.
PharmGKB	PA30734.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q06413.
HOVERGEN	Q06413.
Gene expression databases
ArrayExpress	Q06413.
CleanEx	HS_MEF2C.
GermOnline	ENSG00000081189. Homo sapiens.
Family and domain databases
InterPro	IPR002100. TF_MADSbox. [Graphical view]
Pfam	PF00319. SRF-TF. 1 hit. [Graphical view]
PRINTS	PR00404. MADSDOMAIN.
SMART	SM00432. MADS. 1 hit. [Graphical view]
PROSITE	PS00350. MADS_BOX_1. 1 hit. PS50066. MADS_BOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
LinkHub	Q06413.
NextBio	16578.
SOURCE	Search...

Entry information

Entry name

MEF2C_HUMAN

Accession

Primary (citable) accession number: Q06413

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	November 25, 2008
This is version 69 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)