dbPTM

MK03_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MK03_MOUSE
UniProt AC	Q63844
Protein Name	Mitogen-activated protein kinase 3
Gene Name	Mapk3
Organism	Mus musculus (Mouse).
Sequence Length	380
Subcellular Localization	Cytoplasm. Nucleus. Membrane, caveola . Autophosphorylation at Thr-207 promotes nuclear localization (By similarity). PEA15-binding redirects the biological outcome of MAPK3 kinase-signaling by sequestering MAPK3 into the cytoplasm..
Protein Description	Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade..
Protein Sequence	MAAAAAAPGGGGGEPRGTAGVVPVVPGEVEVVKGQPFDVGPRYTQLQYIGEGAYGMVSSAYDHVRKTRVAIKKISPFEHQTYCQRTLREIQILLRFRHENVIGIRDILRAPTLEAMRDVYIVQDLMETDLYKLLKSQQLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLINTTCDLKICDFGLARIADPEHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINMKARNYLQSLPSKTKVAWAKLFPKSDSKALDLLDRMLTFNPNKRITVEEALAHPYLEQYYDPTDEPVAEEPFTFDMELDDLPKERLKELIFQETARFQPGAPEGP

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MAAAAAAPG ------CCCCCCCCC	13.05	-
18	Phosphorylation	GGGEPRGTAGVVPVV CCCCCCCCCCEECCC	22.86	29514104
33	Acetylation	PGEVEVVKGQPFDVG CCEEEEECCCCCCCC	57.94	23236377
54	Phosphorylation	QYIGEGAYGMVSSAY EEEECCCHHCHHHHH	19.33	25367039
58	Phosphorylation	EGAYGMVSSAYDHVR CCCHHCHHHHHHHHH	10.60	25367039
61	Phosphorylation	YGMVSSAYDHVRKTR HHCHHHHHHHHHHHC	14.45	25367039
128	Phosphorylation	IVQDLMETDLYKLLK HHHHHHHCCHHHHHH	19.83	-
131	Phosphorylation	DLMETDLYKLLKSQQ HHHHCCHHHHHHHCC	11.47	-
171	Phosphorylation	LHRDLKPSNLLINTT CCCCCCHHHEEEEEC	38.22	26239621
177	Phosphorylation	PSNLLINTTCDLKIC HHHEEEEECCCEEEC	23.08	26239621
178	Phosphorylation	SNLLINTTCDLKICD HHEEEEECCCEEECC	10.26	26239621
179	S-palmitoylation	NLLINTTCDLKICDF HEEEEECCCEEECCC	5.62	26165157
199	Phosphorylation	ADPEHDHTGFLTEYV CCCCCCCCCHHHHHH	35.37	26824392
203	Phosphorylation	HDHTGFLTEYVATRW CCCCCHHHHHHHHCC	24.02	27087446
205	Phosphorylation	HTGFLTEYVATRWYR CCCHHHHHHHHCCCC	7.08	27087446
208	Phosphorylation	FLTEYVATRWYRAPE HHHHHHHHCCCCCCE	16.22	25521595
211	Phosphorylation	EYVATRWYRAPEIML HHHHHCCCCCCEEHH	8.13	23608596
220	Phosphorylation	APEIMLNSKGYTKSI CCEEHHCCCCCCCCH	24.40	23608596
221	Ubiquitination	PEIMLNSKGYTKSID CEEHHCCCCCCCCHH	55.66	27667366
264	Phosphorylation	HILGILGSPSQEDLN HHHHHCCCCCHHHHH	20.24	-
266	Phosphorylation	LGILGSPSQEDLNCI HHHCCCCCHHHHHHH	48.15	-
302	Phosphorylation	KLFPKSDSKALDLLD HHCCCCCHHHHHHHH	27.24	-

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
203	T	Phosphorylation	Kinase	MP2K1	P31938	PhosphoELM
203	T	Phosphorylation	Kinase	MEK1	Q01986	PSP
203	T	Phosphorylation	Kinase	MAP2K2	Q63932	Uniprot
205	Y	Phosphorylation	Kinase	MEK1	P31938	PSP
205	Y	Phosphorylation	Kinase	MEK1	Q01986	PSP
205	Y	Phosphorylation	Kinase	MAP2K2	Q63932	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	Map3k1	P53349	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
203	T	Phosphorylation		17947660
Dually phosphorylated on Thr-203 and Tyr-205, which activates the enzyme.

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 MK03_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
GBRR1_HUMAN	GABRR1	physical	12175859
MBP_MOUSE	Mbp	physical	9395235
ELK1_MOUSE	Elk1	physical	10431817
MAP2_MOUSE	Metap2	physical	15544353
MBP_MOUSE	Mbp	physical	15544353
ATF2_MOUSE	Atf2	physical	15192015
MK01_MOUSE	Mapk1	genetic	21505187
NANOG_MOUSE	Nanog	physical	24793005
KS6A3_MOUSE	Rps6ka3	physical	24793005

Drug and Disease Associations

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

Regulatory Network of MK03_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Large scale localization of protein phosphorylation by use ofelectron capture dissociation mass spectrometry."; Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.; Mol. Cell. Proteomics 8:904-912(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-203 AND TYR-205, ANDMASS SPECTROMETRY.	19131326 [Abstract]
"Solid tumor proteome and phosphoproteome analysis by high resolutionmass spectrometry."; Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J.,Faessler R., Mann M.; J. Proteome Res. 7:5314-5326(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-203 AND TYR-205, ANDMASS SPECTROMETRY.	19367708 [Abstract]
"Large-scale identification and evolution indexing of tyrosinephosphorylation sites from murine brain."; Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.; J. Proteome Res. 7:311-318(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-203 AND TYR-205, ANDMASS SPECTROMETRY.	18034455 [Abstract]
"Quantitative time-resolved phosphoproteomic analysis of mast cellsignaling."; Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,Kawakami T., Salomon A.R.; J. Immunol. 179:5864-5876(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-203 AND TYR-205, ANDMASS SPECTROMETRY.	17947660 [Abstract]

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