MEF2A_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: MEF2A_MOUSE
• UniProt AC: Q60929
• Protein Name: Myocyte-specific enhancer factor 2A
• Gene Name: Mef2a
• Organism: Mus musculus (Mouse).
• Sequence Length: 498
• Subcellular Localization: Nucleus.
• Protein Description: Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific genes. Also involved in the activation of numerous growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. In cerebellar granule neurons, phosphorylated and sumoylated MEF2A represses transcription of NUR77 promoting synaptic differentiation. Associates with chromatin to the ZNF16 promoter (By similarity)..
• Protein Sequence: MGRKKIQITRIMDERNRQVTFTKRKFGLMKKAYELSVLCDCEIALIIFNSSNKLFQYASTDMDKVLLKYTEYNEPHESRTNSDIVETLRKKGLNGCESPDADDYFEHSPLSEDRFSKLNEDSDFIFKRGPPGLPPQNFSMSVTVPVTSPNALSYTNPGSSLVSPSLAASSTLADSSMLSPPPATLHRNVSPGAPQRPPSTGSASGMLSTTDLTVPNGAGNSPVGNGFVNSRASPNLIGNTGANSLGKVMPTKSPPPPGGGSLGMNSRKPDLRVVIPPSSKGMMPPLSEEEELELNAQRISSSQATQPLATPVVSVTTPSLPPQGLVYSAMPTAYNTDYSLTSADLSALQGFTSPGMLSLGQASAWQQHHLGQAALSSLVAGGQLSQGSNLSINTNQNINIKSEPISPPRDRMTPSGFQQQQQQPQQQPPPQPPQPQPRQEMGRSPVDSLSSSSSSYDGSDREDPRGDFHSPIVLGRPPNTEDRESPSVKRMRMDTWVT

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
20	Phosphorylation	DERNRQVTFTKRKFG EHHHCEEEECHHHHC	19.76	15735306
23	Ubiquitination	NRQVTFTKRKFGLMK HCEEEECHHHHCCCH	49.77	27667366
59	Phosphorylation	NKLFQYASTDMDKVL CCHHHCCCCCHHHHH	21.72	8663403
82	Phosphorylation	PHESRTNSDIVETLR CCCCCCCHHHHHHHH	28.27	-
98	Phosphorylation	KGLNGCESPDADDYF CCCCCCCCCCHHHCC	31.96	25521595
98 (in isoform 3)	Phosphorylation	-	31.96	25521595
103 (in isoform 3)	Phosphorylation	-	52.30	26745281
104 (in isoform 3)	Phosphorylation	-	16.06	26745281
104	Phosphorylation	ESPDADDYFEHSPLS CCCCHHHCCCCCCCC	16.06	29899451
105 (in isoform 3)	Phosphorylation	-	9.78	26745281
108 (in isoform 3)	Phosphorylation	-	21.97	25521595
108	Phosphorylation	ADDYFEHSPLSEDRF HHHCCCCCCCCHHHH	21.97	25521595
111	Phosphorylation	YFEHSPLSEDRFSKL CCCCCCCCHHHHHHC	40.61	21183079
111 (in isoform 3)	Phosphorylation	-	40.61	25266776
116	Phosphorylation	PLSEDRFSKLNEDSD CCCHHHHHHCCCCCC	36.81	29550500
190	Phosphorylation	ATLHRNVSPGAPQRP CCCCCCCCCCCCCCC	22.59	23649490
199	Phosphorylation	GAPQRPPSTGSASGM CCCCCCCCCCCCCCC	48.35	23649490
200	Phosphorylation	APQRPPSTGSASGML CCCCCCCCCCCCCCE	40.71	26160508
202	Phosphorylation	QRPPSTGSASGMLST CCCCCCCCCCCCEEC	21.25	26160508
204	Phosphorylation	PPSTGSASGMLSTTD CCCCCCCCCCEECCC	26.82	26160508
208	Phosphorylation	GSASGMLSTTDLTVP CCCCCCEECCCEECC	21.99	26160508
209	Phosphorylation	SASGMLSTTDLTVPN CCCCCEECCCEECCC	21.99	26160508
210	Phosphorylation	ASGMLSTTDLTVPNG CCCCEECCCEECCCC	26.15	26160508
213	Phosphorylation	MLSTTDLTVPNGAGN CEECCCEECCCCCCC	36.41	26160508
221	Phosphorylation	VPNGAGNSPVGNGFV CCCCCCCCCCCCCCC	21.75	23649490
233	Phosphorylation	GFVNSRASPNLIGNT CCCCCCCCCCCCCCC	17.14	25521595
240	Phosphorylation	SPNLIGNTGANSLGK CCCCCCCCCCCCCCC	32.24	25619855
244	Phosphorylation	IGNTGANSLGKVMPT CCCCCCCCCCCCCCC	37.65	25619855
247	Acetylation	TGANSLGKVMPTKSP CCCCCCCCCCCCCCC	40.42	23806337
251	Phosphorylation	SLGKVMPTKSPPPPG CCCCCCCCCCCCCCC	26.51	26239621
253	Phosphorylation	GKVMPTKSPPPPGGG CCCCCCCCCCCCCCC	45.15	25521595
261	Phosphorylation	PPPPGGGSLGMNSRK CCCCCCCCCCCCCCC	25.65	25266776
266	Phosphorylation	GGSLGMNSRKPDLRV CCCCCCCCCCCCEEE	32.56	23984901
310	Phosphorylation	QATQPLATPVVSVTT CCCCCCCCCEEEEEC	25.05	17785444
317	Phosphorylation	TPVVSVTTPSLPPQG CCEEEEECCCCCCCC	14.55	-
353	Phosphorylation	SALQGFTSPGMLSLG HHHCCCCCCCCHHHH	19.73	-
401	Acetylation	TNQNINIKSEPISPP CCCCCCCCCCCCCCC	44.25	-
402	Phosphorylation	NQNINIKSEPISPPR CCCCCCCCCCCCCCC	44.82	26160508
406	Phosphorylation	NIKSEPISPPRDRMT CCCCCCCCCCCCCCC	39.30	26824392
413	Phosphorylation	SPPRDRMTPSGFQQQ CCCCCCCCCCHHHHH	18.39	26160508
415	Phosphorylation	PRDRMTPSGFQQQQQ CCCCCCCCHHHHHHC	42.97	26160508
444	Phosphorylation	PRQEMGRSPVDSLSS CCCCCCCCCCHHHCC	24.44	28066266
448	Phosphorylation	MGRSPVDSLSSSSSS CCCCCCHHHCCCCCC	30.31	28066266
470	Phosphorylation	DPRGDFHSPIVLGRP CCCCCCCCCCCCCCC	19.13	27742792
480	Phosphorylation	VLGRPPNTEDRESPS CCCCCCCCCCCCCCC	45.07	21743459
485	Phosphorylation	PNTEDRESPSVKRMR CCCCCCCCCCHHCCC	24.30	26824392
487	Phosphorylation	TEDRESPSVKRMRMD CCCCCCCCHHCCCCC	49.93	28066266

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	-	Uniprot
310	T	Phosphorylation	Kinase	NLK	O54949	Uniprot
317	T	Phosphorylation	Kinase	MAPK7	Q9WVS8	Uniprot
353	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.	-
98	S	Phosphorylation	Isoform 3 is phosphorylated on Ser-98 and Thr-108.	17242355
108	T	Phosphorylation	Isoform 3 is phosphorylated on Ser-98 and Thr-108.	17242355
312	T	Phosphorylation	Phosphorylation on Thr-312, Thr-319 and Ser-355 can be induced by EGF (By similarity).	17785444
312	T	Phosphorylation	Phosphorylation on Thr-312 and Thr-319 are the main sites involved in p38 MAPK signaling and activate transcription.	17785444
319	T	Phosphorylation	Phosphorylation on Thr-312, Thr-319 and Ser-355 can be induced by EGF (By similarity).	17785444
319	T	Phosphorylation	Phosphorylation on Thr-312 and Thr-319 are the main sites involved in p38 MAPK signaling and activate transcription.	17785444
355	S	Phosphorylation	Phosphorylation on Thr-312, Thr-319 and Ser-355 can be induced by EGF (By similarity).	17785444
401	K	Acetylation	Acetylation on Lys-401 activates transcriptional activity.	-
401	K	Sumoylation	Sumoylation on Lys-401 is enhanced by PIAS1 and represses transcriptional activity.	-
401	K	Sumoylation	Constitutive phosphorylation on Ser-406 promotes Lys-401 sumoylation thus preventing acetylation at this site.	17785444
401	K	Phosphorylation	Constitutive phosphorylation on Ser-406 promotes Lys-401 sumoylation thus preventing acetylation at this site.	17785444
401	K	Acetylation	Constitutive phosphorylation on Ser-406 promotes Lys-401 sumoylation thus preventing acetylation at this site.	17785444
403	K	Sumoylation	Dephosphorylation on Ser-406 by PPP3CA upon neuron depolarization promotes a switch from sumoylation to acetylation on residue Lys-403 leading to inhibition of dendrite claw differentiation.	17785444
403	K	Phosphorylation	Dephosphorylation on Ser-406 by PPP3CA upon neuron depolarization promotes a switch from sumoylation to acetylation on residue Lys-403 leading to inhibition of dendrite claw differentiation.	17785444
403	K	Acetylation	Dephosphorylation on Ser-406 by PPP3CA upon neuron depolarization promotes a switch from sumoylation to acetylation on residue Lys-403 leading to inhibition of dendrite claw differentiation.	17785444
406	S	Acetylation	Constitutive phosphorylation on Ser-406 promotes Lys-401 sumoylation thus preventing acetylation at this site.	17785444
406	S	Acetylation	Dephosphorylation on Ser-406 by PPP3CA upon neuron depolarization promotes a switch from sumoylation to acetylation on residue Lys-403 leading to inhibition of dendrite claw differentiation.	17785444
406	S	Phosphorylation	Constitutive phosphorylation on Ser-406 promotes Lys-401 sumoylation thus preventing acetylation at this site.	17785444
406	S	Phosphorylation	Dephosphorylation on Ser-406 by PPP3CA upon neuron depolarization promotes a switch from sumoylation to acetylation on residue Lys-403 leading to inhibition of dendrite claw differentiation.	17785444
406	S	Phosphorylation	Phosphorylation on Ser-406 is required for sumoylation.	-
406	S	Sumoylation	Constitutive phosphorylation on Ser-406 promotes Lys-401 sumoylation thus preventing acetylation at this site.	17785444
406	S	Sumoylation	Dephosphorylation on Ser-406 by PPP3CA upon neuron depolarization promotes a switch from sumoylation to acetylation on residue Lys-403 leading to inhibition of dendrite claw differentiation.	17785444
406	S	Sumoylation	Phosphorylation on Ser-406 is required for sumoylation.	-
408	S	Phosphorylation	Phosphorylation on Ser-408 by CDK5 induced by neurotoxicity inhibits MEF2A transcriptional activation leading to apoptosis of cortical neurons.	17785444

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of MEF2A_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SMAD2_MOUSE	Smad2	physical	11160896

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"Large-scale phosphorylation analysis of mouse liver.";
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98 (ISOFORM 1),PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98 AND THR-108 (ISOFORM3), AND MASS SPECTROMETRY.
PubMed: 17242355

"Nemo-like kinase-myocyte enhancer factor 2A signaling regulatesanterior formation in Xenopus development.";
Satoh K., Ohnishi J., Sato A., Takeyama M., Iemura S., Natsume T.,Shibuya H.;
Mol. Cell. Biol. 27:7623-7630(2007).
Cited for: INTERACTION WITH NLK, AND PHOSPHORYLATION AT THR-310.
PubMed: 17785444