MEF2C_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: MEF2C_MOUSE
• UniProt AC: Q8CFN5
• Protein Name: Myocyte-specific enhancer factor 2C {ECO:0000305}
• Gene Name: Mef2c {ECO:0000312|MGI:MGI:99458}
• Organism: Mus musculus (Mouse).
• Sequence Length: 474
• 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. May also be involved in neurogenesis and in the development of cortical architecture. Isoform 3 and isoform 4, which lack the repressor domain, are more active than isoform 1, isoform 2 and isoform 5 (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..
• Protein Sequence: MGRKKIQITRIMDERNRQVTFTKRKFGLMKKAYELSVLCDCEIALIIFNSTNKLFQYASTDMDKVLLKYTEYNEPHESRTNSDIVETLRKKGLNGCDSPDPDADDSVGHSPESEDKYRKINEDIDLMISRQRLCAVPPPSFEMPVTIPVSSHNSLVYSNPVSTLGNPNLLPLAHPSLQRNSMSPGVTHRPPSAGNTGGLMGGDLTSGAGTSAGNGYGNPRNSPGLLVSPGNLNKNIQAKSPPPMNLGMNNRKPDLRVLIPPGSKNTMPSVSEDVDLLLNQRINNSQSAQSLATPVVSVATPTLPGQGMGGYPSAISTTYGTEYSLSSADLSSLSGFNTASALHLGSVTGWQQQHLHNMPPSALSQLGACTSTHLSQSSNLSLPSTQSLSIKSEPVSPPRDRTTTPSRYPQHTTRHEAGRSPVDSLSSCSSSYDGSDREDHRNEFHSPIGLTRPSPDERESPSVKRMRLSEGWAT

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
4	Acetylation	----MGRKKIQITRI ----CCCCEEEEEEE	48.80	18086704
9	O-linked_Glycosylation	GRKKIQITRIMDERN CCCEEEEEEEEEHHH	9.58	26160456
20	Phosphorylation	DERNRQVTFTKRKFG EHHHCEEEECHHHHC	19.76	15735306
59	Phosphorylation	NKLFQYASTDMDKVL CHHHHHCCCCHHHHH	21.72	8663403
82	Phosphorylation	PHESRTNSDIVETLR CCCCCCCHHHHHHHH	28.27	-
96 (in isoform 5)	Phosphorylation	-	4.57	24899341
96 (in isoform 4)	Phosphorylation	-	4.57	24899341
98	Phosphorylation	KGLNGCDSPDPDADD CCCCCCCCCCCCCCC	34.97	25521595
98 (in isoform 5)	Phosphorylation	-	34.97	24704852
98 (in isoform 4)	Phosphorylation	-	34.97	24704852
103 (in isoform 5)	Phosphorylation	-	28.09	26643407
103 (in isoform 4)	Phosphorylation	-	28.09	26643407
104 (in isoform 5)	Phosphorylation	-	56.98	26643407
104 (in isoform 4)	Phosphorylation	-	56.98	26643407
105 (in isoform 4)	Phosphorylation	-	47.12	26643407
105 (in isoform 5)	Phosphorylation	-	47.12	26643407
106	Phosphorylation	PDPDADDSVGHSPES CCCCCCCCCCCCCCC	30.46	25521595
108 (in isoform 4)	Phosphorylation	-	21.36	24899341
108 (in isoform 5)	Phosphorylation	-	21.36	24899341
110	Phosphorylation	ADDSVGHSPESEDKY CCCCCCCCCCCHHHH	25.16	25521595
111 (in isoform 4)	Phosphorylation	-	43.38	26643407
111 (in isoform 5)	Phosphorylation	-	43.38	26643407
113	Phosphorylation	SVGHSPESEDKYRKI CCCCCCCCHHHHHHH	55.25	19060867
116	Acetylation	HSPESEDKYRKINED CCCCCHHHHHHHHHH	42.79	-
117	Phosphorylation	SPESEDKYRKINEDI CCCCHHHHHHHHHHH	29.47	25367039
119	Acetylation	ESEDKYRKINEDIDL CCHHHHHHHHHHHHH	46.95	-
183	Phosphorylation	SLQRNSMSPGVTHRP HHCCCCCCCCCCCCC	20.51	21183079
187	Phosphorylation	NSMSPGVTHRPPSAG CCCCCCCCCCCCCCC	20.34	21183079
192	Phosphorylation	GVTHRPPSAGNTGGL CCCCCCCCCCCCCCC	52.03	22942356
196	Phosphorylation	RPPSAGNTGGLMGGD CCCCCCCCCCCCCCC	31.54	22807455
205	Phosphorylation	GLMGGDLTSGAGTSA CCCCCCCCCCCCCCC	29.83	22807455
206	Phosphorylation	LMGGDLTSGAGTSAG CCCCCCCCCCCCCCC	33.66	22942356
222	Phosphorylation	GYGNPRNSPGLLVSP CCCCCCCCCCEEECC	22.94	25521595
222	O-linked_Glycosylation	GYGNPRNSPGLLVSP CCCCCCCCCCEEECC	22.94	26160456
228	Phosphorylation	NSPGLLVSPGNLNKN CCCCEEECCCCCCCC	27.36	22942356
234	Acetylation	VSPGNLNKNIQAKSP ECCCCCCCCCCCCCC	59.60	-
239	Acetylation	LNKNIQAKSPPPMNL CCCCCCCCCCCCCCC	47.31	-
240	Phosphorylation	NKNIQAKSPPPMNLG CCCCCCCCCCCCCCC	45.73	23527152
251	Methylation	MNLGMNNRKPDLRVL CCCCCCCCCCCEEEE	47.05	30988083
252	Acetylation	NLGMNNRKPDLRVLI CCCCCCCCCCEEEEE	45.03	-
264	Acetylation	VLIPPGSKNTMPSVS EEECCCCCCCCCCHH	63.45	-
269	O-linked_Glycosylation	GSKNTMPSVSEDVDL CCCCCCCCHHHHHHH	27.70	26160456
293	Phosphorylation	QSAQSLATPVVSVAT HHHHHHCCCEEEEEC	23.16	-
300	Phosphorylation	TPVVSVATPTLPGQG CCEEEEECCCCCCCC	18.04	-
396	Phosphorylation	SIKSEPVSPPRDRTT EEECCCCCCCCCCCC	39.64	30635358
402	Phosphorylation	VSPPRDRTTTPSRYP CCCCCCCCCCCCCCC	39.03	26643407
403	Phosphorylation	SPPRDRTTTPSRYPQ CCCCCCCCCCCCCCC	37.29	26643407
404	Phosphorylation	PPRDRTTTPSRYPQH CCCCCCCCCCCCCCC	20.75	26643407
406	Phosphorylation	RDRTTTPSRYPQHTT CCCCCCCCCCCCCCC	42.21	26643407
408	Phosphorylation	RTTTPSRYPQHTTRH CCCCCCCCCCCCCCC	16.16	26643407
420	Phosphorylation	TRHEAGRSPVDSLSS CCCCCCCCCCCCHHH	28.49	-
446	Phosphorylation	DHRNEFHSPIGLTRP HHCCCCCCCCCCCCC	24.43	26370283
451	Phosphorylation	FHSPIGLTRPSPDER CCCCCCCCCCCCCCC	35.01	25338131
454	Phosphorylation	PIGLTRPSPDERESP CCCCCCCCCCCCCCC	41.51	26370283
460	Phosphorylation	PSPDERESPSVKRMR CCCCCCCCCCHHEEE	28.79	27742792
462	Phosphorylation	PDERESPSVKRMRLS CCCCCCCCHHEEECC	49.93	21183079
469	Phosphorylation	SVKRMRLSEGWAT-- CHHEEECCCCCCC--	24.57	22942356

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
20	T	Phosphorylation	Kinase	PRKACA	P17612	GPS
20	T	Phosphorylation	Kinase	KAPCA	P05132	PhosphoELM
59	S	Phosphorylation	Kinase	CSNK2A1	Q60737	GPS
59	S	Phosphorylation	Kinase	CK2-FAMILY	-	GPS
59	S	Phosphorylation	Kinase	CK2	-	Uniprot
293	T	Phosphorylation	Kinase	MAPK14	P47811	Uniprot
300	T	Phosphorylation	Kinase	MAPK14	P47811	Uniprot
396	S	Phosphorylation	Kinase	CDK5	P49615	Uniprot
420	S	Phosphorylation	Kinase	MAPK7	Q9WVS8	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
4	K	Acetylation	Acetylation on Lys-4 increases DNA binding and transactivation.	18086704
59	S	Phosphorylation	Phosphorylation on Ser-59 enhances DNA binding activity (By similarity).	8663403
391	K	Phosphorylation	Phosphorylation on Ser-396 is required for Lys-391 sumoylation and inhibits transcriptional activity.	8663403
391	K	Sumoylation	Phosphorylation on Ser-396 is required for Lys-391 sumoylation and inhibits transcriptional activity.	8663403
391	K	Sumoylation	Sumoylated on Lys-391 with SUMO2 but not by SUMO1 represses transcriptional activity.	-
396	S	Phosphorylation	Phosphorylation on Ser-396 is required for Lys-391 sumoylation and inhibits transcriptional activity.	8663403
396	S	Sumoylation	Phosphorylation on Ser-396 is required for Lys-391 sumoylation and inhibits transcriptional activity.	8663403

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of MEF2C_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
NCOA2_MOUSE	Ncoa2	physical	20211142
IFRD1_MOUSE	Ifrd1	physical	15743821
KDM1A_HUMAN	KDM1A	physical	20833138
NKX25_MOUSE	Nkx2-5	physical	19035347

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Acetylation

"Differentiation-dependent lysine 4 acetylation enhances MEF2C bindingto DNA in skeletal muscle cells.";
Angelelli C., Magli A., Ferrari D., Ganassi M., Matafora V.,Parise F., Razzini G., Bachi A., Ferrari S., Molinari S.;
Nucleic Acids Res. 36:915-928(2008).
Cited for: ACETYLATION AT LYS-4, DNA-BINDING, MASS SPECTROMETRY, FUNCTION, ANDMUTAGENESIS OF ARG-3 AND LYS-4.
PubMed: 18086704

Phosphorylation

"Phosphorylation of the MADS-Box transcription factor MEF2C enhancesits DNA binding activity.";
Molkentin J.D., Li L., Olson E.N.;
J. Biol. Chem. 271:17199-17204(1996).
Cited for: PHOSPHORYLATION AT SER-59, AND MUTAGENESIS OF SER-59.
PubMed: 8663403