dbPTM

MEF2C_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MEF2C_HUMAN
UniProt AC	Q06413
Protein Name	Myocyte-specific enhancer factor 2C {ECO:0000305}
Gene Name	MEF2C {ECO:0000312\|HGNC:HGNC:6996}
Organism	Homo sapiens (Human).
Sequence Length	473
Subcellular Localization	Nucleus . Cytoplasm, sarcoplasm .
Protein Description	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..
Protein Sequence	MGRKKIQITRIMDERNRQVTFTKRKFGLMKKAYELSVLCDCEIALIIFNSTNKLFQYASTDMDKVLLKYTEYNEPHESRTNSDIVETLRKKGLNGCDSPDPDADDSVGHSPESEDKYRKINEDIDLMISRQRLCAVPPPNFEMPVSIPVSSHNSLVYSNPVSSLGNPNLLPLAHPSLQRNSMSPGVTHRPPSAGNTGGLMGGDLTSGAGTSAGNGYGNPRNSPGLLVSPGNLNKNMQAKSPPPMNLGMNNRKPDLRVLIPPGSKNTMPSVSEDVDLLLNQRINNSQSAQSLATPVVSVATPTLPGQGMGGYPSAISTTYGTEYSLSSADLSSLSGFNTASALHLGSVTGWQQQHLHNMPPSALSQLGACTSTHLSQSSNLSLPSTQSLNIKSEPVSPPRDRTTTPSRYPQHTRHEAGRSPVDSLSSCSSSYDGSDREDHRNEFHSPIGLTRPSPDERESPSVKRMRLSEGWAT

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
4	Acetylation	----MGRKKIQITRI ----CCCCEEEEEEE	48.80	-
23	Ubiquitination	NRQVTFTKRKFGLMK HCEEEECHHHHCCCH	49.77	-
59	Phosphorylation	NKLFQYASTDMDKVL CHHHHHCCCCHHHHH	21.72	8663403
64	Ubiquitination	YASTDMDKVLLKYTE HCCCCHHHHHHHHHC	28.30	21890473
64	Ubiquitination	YASTDMDKVLLKYTE HCCCCHHHHHHHHHC	28.30	-
64 (in isoform 3)	Ubiquitination	-	28.30	21890473
64 (in isoform 2)	Ubiquitination	-	28.30	21890473
64 (in isoform 1)	Ubiquitination	-	28.30	21890473
68	Ubiquitination	DMDKVLLKYTEYNEP CHHHHHHHHHCCCCC	46.06	21890473
68	Ubiquitination	DMDKVLLKYTEYNEP CHHHHHHHHHCCCCC	46.06	-
68 (in isoform 1)	Ubiquitination	-	46.06	21890473
68 (in isoform 2)	Ubiquitination	-	46.06	21890473
68 (in isoform 3)	Ubiquitination	-	46.06	21890473
69	Phosphorylation	MDKVLLKYTEYNEPH HHHHHHHHHCCCCCC	12.55	26657352
70	Phosphorylation	DKVLLKYTEYNEPHE HHHHHHHHCCCCCCC	30.33	26657352
78	Phosphorylation	EYNEPHESRTNSDIV CCCCCCCCCCCHHHH	41.17	26657352
80	Phosphorylation	NEPHESRTNSDIVET CCCCCCCCCHHHHHH	48.64	-
82	Phosphorylation	PHESRTNSDIVETLR CCCCCCCHHHHHHHH	28.27	30108239
87	Phosphorylation	TNSDIVETLRKKGLN CCHHHHHHHHHCCCC	22.44	-
98 (in isoform 6)	Phosphorylation	-	34.97	26657352
98	Phosphorylation	KGLNGCDSPDPDADD CCCCCCCCCCCCCCC	34.97	23401153
103 (in isoform 6)	Phosphorylation	-	28.09	25954137
104 (in isoform 6)	Phosphorylation	-	56.98	27251275
105 (in isoform 6)	Phosphorylation	-	47.12	-
106	Phosphorylation	PDPDADDSVGHSPES CCCCCCCCCCCCCCC	30.46	23403867
108 (in isoform 6)	Phosphorylation	-	21.36	28450419
110	Phosphorylation	ADDSVGHSPESEDKY CCCCCCCCCCCHHHH	25.16	23401153
113	Phosphorylation	SVGHSPESEDKYRKI CCCCCCCCHHHHHHH	55.25	23403867
116	Acetylation	HSPESEDKYRKINED CCCCCHHHHHHHHHH	42.79	15831463
118 (in isoform 5)	Phosphorylation	-	38.83	26657352
119	Acetylation	ESEDKYRKINEDIDL CCHHHHHHHHHHHHH	46.95	15831463
123 (in isoform 5)	Phosphorylation	-	34.90	25954137
124 (in isoform 5)	Phosphorylation	-	3.41	27251275
125 (in isoform 5)	Phosphorylation	-	42.37	-
128 (in isoform 5)	Phosphorylation	-	3.90	28450419
176	Phosphorylation	LLPLAHPSLQRNSMS CCCCCCHHHCCCCCC	27.54	26091039
181	Phosphorylation	HPSLQRNSMSPGVTH CHHHCCCCCCCCCCC	23.87	30108239
183	Phosphorylation	SLQRNSMSPGVTHRP HHCCCCCCCCCCCCC	20.51	23401153
187	Phosphorylation	NSMSPGVTHRPPSAG CCCCCCCCCCCCCCC	20.34	30108239
192	Phosphorylation	GVTHRPPSAGNTGGL CCCCCCCCCCCCCCC	52.03	30108239
196	Phosphorylation	RPPSAGNTGGLMGGD CCCCCCCCCCCCCCC	31.54	30108239
205	Phosphorylation	GLMGGDLTSGAGTSA CCCCCCCCCCCCCCC	29.83	27080861
206	Phosphorylation	LMGGDLTSGAGTSAG CCCCCCCCCCCCCCC	33.66	27080861
210 (in isoform 5)	Phosphorylation	-	18.18	27251275
222	Phosphorylation	GYGNPRNSPGLLVSP CCCCCCCCCCEEECC	22.94	23401153
228	Phosphorylation	NSPGLLVSPGNLNKN CCCCEEECCCCCCCC	27.36	23401153
234	Acetylation	VSPGNLNKNMQAKSP ECCCCCCCCCCCCCC	57.89	15831463
239	Acetylation	LNKNMQAKSPPPMNL CCCCCCCCCCCCCCC	46.75	15831463
240 (in isoform 5)	Phosphorylation	-	45.73	27251275
240	Phosphorylation	NKNMQAKSPPPMNLG CCCCCCCCCCCCCCC	45.73	23401153
246 (in isoform 5)	Phosphorylation	-	5.83	27251275
252	Acetylation	NLGMNNRKPDLRVLI CCCCCCCCCCEEEEE	45.03	15831463
258 (in isoform 5)	Phosphorylation	-	3.83	27251275
264	Acetylation	VLIPPGSKNTMPSVS EEECCCCCCCCCCHH	63.45	15831463
271	O-linked_Glycosylation	KNTMPSVSEDVDLLL CCCCCCHHHHHHHHH	32.20	28314751
293	Phosphorylation	QSAQSLATPVVSVAT HHHHHHCCCEEEEEC	23.16	9384584
300	Phosphorylation	TPVVSVATPTLPGQG CCEEEEECCCCCCCC	18.04	9384584
387	Phosphorylation	LSLPSTQSLNIKSEP CCCCCCCCCCCCCCC	24.38	9384584
391	Sumoylation	STQSLNIKSEPVSPP CCCCCCCCCCCCCCC	47.93	15743823
391	Sumoylation	STQSLNIKSEPVSPP CCCCCCCCCCCCCCC	47.93	-
392	Phosphorylation	TQSLNIKSEPVSPPR CCCCCCCCCCCCCCC	43.25	23403867
396	Phosphorylation	NIKSEPVSPPRDRTT CCCCCCCCCCCCCCC	39.64	23401153
402	Phosphorylation	VSPPRDRTTTPSRYP CCCCCCCCCCCCCCC	39.03	24719451
403	Phosphorylation	SPPRDRTTTPSRYPQ CCCCCCCCCCCCCCC	37.29	30301811
404	Phosphorylation	PPRDRTTTPSRYPQH CCCCCCCCCCCCCCC	20.75	28450419
406	Phosphorylation	RDRTTTPSRYPQHTR CCCCCCCCCCCCCCC	42.21	30301811
406 (in isoform 5)	Phosphorylation	-	42.21	27251275
408	Phosphorylation	RTTTPSRYPQHTRHE CCCCCCCCCCCCCCC	16.16	30301811
412	Phosphorylation	PSRYPQHTRHEAGRS CCCCCCCCCCCCCCC	28.59	30301811
414 (in isoform 5)	Phosphorylation	-	30.34	27251275
419	Phosphorylation	TRHEAGRSPVDSLSS CCCCCCCCCCCCHHH	28.49	28192239
423	Phosphorylation	AGRSPVDSLSSCSSS CCCCCCCCHHHCCCC	30.31	27251275
425	Phosphorylation	RSPVDSLSSCSSSYD CCCCCCHHHCCCCCC	33.00	29449344
426	Phosphorylation	SPVDSLSSCSSSYDG CCCCCHHHCCCCCCC	24.26	29449344
428	Phosphorylation	VDSLSSCSSSYDGSD CCCHHHCCCCCCCCC	25.02	29449344
429 (in isoform 5)	Phosphorylation	-	36.93	27251275
429	Phosphorylation	DSLSSCSSSYDGSDR CCHHHCCCCCCCCCC	36.93	29449344
430	Phosphorylation	SLSSCSSSYDGSDRE CHHHCCCCCCCCCCH	15.79	29449344
431	Phosphorylation	LSSCSSSYDGSDRED HHHCCCCCCCCCCHH	26.69	29449344
445	Phosphorylation	DHRNEFHSPIGLTRP HHCCCCCCCCCCCCC	24.43	23401153
450	Phosphorylation	FHSPIGLTRPSPDER CCCCCCCCCCCCCCC	35.01	26657352
453	Phosphorylation	PIGLTRPSPDERESP CCCCCCCCCCCCCCC	41.51	26307563
459	Phosphorylation	PSPDERESPSVKRMR CCCCCCCCCCHHEEE	28.79	26657352
461	Phosphorylation	PDERESPSVKRMRLS CCCCCCCCHHEEECC	49.93	30108239
469 (in isoform 5)	Phosphorylation	-	64.44	27251275

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
59	S	Phosphorylation	Kinase	CK2_GROUP	-	PhosphoELM
59	S	Phosphorylation	Kinase	CK2	-	Uniprot
59	S	Phosphorylation	Kinase	CK2-FAMILY	-	GPS
80	T	Phosphorylation	Kinase	CAMLCK	Q32MK0	PSP
80	T	Phosphorylation	Kinase	MYLK2	Q9H1R3	GPS
192	S	Phosphorylation	Kinase	RPS6KA3	P51812	GPS
222	S	Phosphorylation	Kinase	MARK3	P27448	PSP
293	T	Phosphorylation	Kinase	MK14	Q16539	PhosphoELM
293	T	Phosphorylation	Kinase	MAPK14	Q16539	GPS
300	T	Phosphorylation	Kinase	MK14	Q16539	PhosphoELM
300	T	Phosphorylation	Kinase	MAPK14	Q16539	GPS
387	S	Phosphorylation	Kinase	MAPK_GROUP	-	PhosphoELM
387	S	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS
387	S	Phosphorylation	Kinase	MAPK14	Q16539	GPS
387	S	Phosphorylation	Kinase	MAPK7	Q13164	GPS
387	S	Phosphorylation	Kinase	MAPK7	Q13164	GPS
396	S	Phosphorylation	Kinase	CDK5	Q00535	Uniprot
396	S	Phosphorylation	Kinase	CDK1	P06493	PSP
419	S	Phosphorylation	Kinase	MAPK7	Q13164	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
4	K	Acetylation	-
Acetylation on Lys-4 increases DNA binding and transactivation (By similarity).
59	S	Phosphorylation	9384584
Phosphorylation on Ser-59 enhances DNA binding activity (By similarity).
391	K	Phosphorylation	15743823
Phosphorylation on Ser-396 is required for Lys-391 sumoylation and inhibits transcriptional activity.
391	K	Sumoylation	15743823
Phosphorylation on Ser-396 is required for Lys-391 sumoylation and inhibits transcriptional activity.
391	K	Sumoylation	15743823
Sumoylated on Lys-391 with SUMO2 but not by SUMO1 represses transcriptional activity.
396	S	Phosphorylation	15340086
Phosphorylation on Ser-396 is required for Lys-391 sumoylation and inhibits transcriptional activity.
396	S	Sumoylation	15340086
Phosphorylation on Ser-396 is required for Lys-391 sumoylation and inhibits transcriptional activity.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of MEF2C_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
HDAC4_HUMAN	HDAC4	physical	10523670
HDAC4_HUMAN	HDAC4	physical	11486037
EP300_HUMAN	EP300	genetic	9001254
EP300_HUMAN	EP300	physical	9001254
SP1_HUMAN	SP1	physical	9748305
SOX18_HUMAN	SOX18	physical	11554755
TEAD1_HUMAN	TEAD1	physical	12061776
MYOG_HUMAN	MYOG	physical	8548800
EPAS1_HUMAN	EPAS1	physical	20936779
MK07_HUMAN	MAPK7	physical	20936779
SPTB2_HUMAN	SPTBN1	physical	20936779
1433Z_HUMAN	YWHAZ	physical	20936779
HDAC9_HUMAN	HDAC9	physical	20936779
CSN5_HUMAN	COPS5	physical	20936779
HDAC9_HUMAN	HDAC9	physical	20211142
HDAC4_HUMAN	HDAC4	physical	12709441
HDAC7_HUMAN	HDAC7	physical	18463162
NCOA2_HUMAN	NCOA2	physical	12130539
IFRD1_HUMAN	IFRD1	physical	15743821
HDAC4_HUMAN	HDAC4	physical	15743821
HDAC4_HUMAN	HDAC4	physical	11279209
HDAC5_HUMAN	HDAC5	physical	11279209
HDAC7_HUMAN	HDAC7	physical	11279209
PG12A_HUMAN	PLA2G12A	physical	21988832
SKP2_HUMAN	SKP2	physical	25733682
MEF2C_HUMAN	MEF2C	physical	11744164

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
613443	Mental retardation, autosomal dominant 20 (MRD20)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of MEF2C_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"Myocyte enhancer factor 2 acetylation by p300 enhances its DNAbinding activity, transcriptional activity, and myogenicdifferentiation."; Ma K., Chan J.K., Zhu G., Wu Z.; Mol. Cell. Biol. 25:3575-3582(2005). Cited for: ACETYLATION AT LYS-116; LYS-119; LYS-234; LYS-239; LYS-252 ANDLYS-264, INTERACTION WITH EP300, FUNCTION, DNA-BINDING, ANDMUTAGENESIS OF LYS-116; LYS-119; LYS-234; LYS-239; LYS-252 ANDLYS-264.	15831463 [Abstract]
Phosphorylation
Reference	PubMed
"Phosphorylation and alternative pre-mRNA splicing converge toregulate myocyte enhancer factor 2C activity."; Zhu B., Gulick T.; Mol. Cell. Biol. 24:8264-8275(2004). Cited for: PHOSPHORYLATION AT SER-396, MASS SPECTROMETRY, MUTAGENESIS OF SER-396,AND FUNCTION OF ISOFORMS.	15340086 [Abstract]
"Activation of the transcription factor MEF2C by the MAP kinase p38 ininflammation."; Han J., Jiang Y., Li Z., Kravchenko V.V., Ulevitch R.J.; Nature 386:296-299(1997). Cited for: PHOSPHORYLATION AT THR-293; THR-300 AND SER-419, FUNCTION, ANDMUTAGENESIS OF THR-293; THR-300 AND SER-419.	9069290 [Abstract]
"BMK1/ERK5 regulates serum-induced early gene expression throughtranscription factor MEF2C."; Kato Y., Kravchenko V.V., Tapping R.I., Han J., Ulevitch R.J.,Lee J.-D.; EMBO J. 16:7054-7066(1997). Cited for: PHOSPHORYLATION AT THR-293; THR-300 AND SER-419, FUNCTION, ANDMUTAGENESIS OF THR-293; THR-300 AND SER-419.	9384584 [Abstract]
Sumoylation
Reference	PubMed
"Phosphorylation-facilitated sumoylation of MEF2C negatively regulatesits transcriptional activity."; Kang J., Gocke C.B., Yu H.; BMC Biochem. 7:5-5(2006). Cited for: SUMOYLATION AT LYS-391, AND MUTAGENESIS OF LYS-391 AND SER-396.	16478538 [Abstract]
"Association with class IIa histone deacetylases upregulates thesumoylation of MEF2 transcription factors."; Gregoire S., Yang X.-J.; Mol. Cell. Biol. 25:2273-2287(2005). Cited for: SUMOYLATION AT LYS-391.	15743823 [Abstract]

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