MK03_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: MK03_RAT
• UniProt AC: P21708
• Protein Name: Mitogen-activated protein kinase 3
• Gene Name: Mapk3
• Organism: Rattus norvegicus (Rat).
• Sequence Length: 380
• Subcellular Localization: Cytoplasm . Nucleus. Membrane, caveola . Autophosphorylation at Thr-207 promotes nuclear localization. PEA15-binding redirects the biological outcome of MAPK3 kinase-signaling by sequestering MAPK3 into the cytoplasm..; Isoform 2: Nucleus.
• 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: MAAAAAAPGGGGGEPRGTAGVVPVVPGEVEVVKGQPFDVGPRYTQLQYIGEGAYGMVSSAYDHVRKTRVAIKKISPFEHQTYCQRTLREIQILLRFRHENVIGIRDILRAPTLEAMRDVYIVQDLMETDLYKLLKSQQLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLINTTCDLKICDFGLARIADPEHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINMKARNYLQSLPSKTKVAWAKLFPKSDSKALDLLDRMLTFNPNKRITVEEALAHPYLEQYYDPTDEPVAEEPFTFDMELDDLPKERLKELIFQETARFQPGAPEAP

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
2	Acetylation	------MAAAAAAPG ------CCCCCCCCC	13.05	-
61	Phosphorylation	YGMVSSAYDHVRKTR HHCHHHHHHHHHHHC	14.45	-
156	Acetylation	YQILRGLKYIHSANV HHHHHHCHHHHHCCC	45.01	-
179	S-nitrosylation	NLLINTTCDLKICDF HEEEEECCCEEECCC	5.62	16418269
179	S-nitrosocysteine	NLLINTTCDLKICDF HEEEEECCCEEECCC	5.62	-
199	Phosphorylation	ADPEHDHTGFLTEYV CCCCCCCCCHHHHHH	35.37	27097102
203	Phosphorylation	HDHTGFLTEYVATRW CCCCCHHHHHHHHCC	24.02	18757826
205	Phosphorylation	HTGFLTEYVATRWYR CCCHHHHHHHHCCCC	7.08	18757826
208	Phosphorylation	FLTEYVATRWYRAPE HHHHHHHHCCCCCCE	16.22	27097102
223	Phosphorylation	IMLNSKGYTKSIDIW EHHCCCCCCCCHHHH	18.09	-
224	Phosphorylation	MLNSKGYTKSIDIWS HHCCCCCCCCHHHHH	27.30	-
264	Phosphorylation	HILGILGSPSQEDLN HHHHHCCCCCHHHHH	20.24	-
266	Phosphorylation	LGILGSPSQEDLNCI HHHCCCCCHHHHHHH	48.15	-
284	Phosphorylation	KARNYLQSLPSKTKV HHHHHHHCCCCCCCE	39.39	23984901
295	Acetylation	KTKVAWAKLFPKSDS CCCEEHHHHCCCCCH	39.70	22902405
302	Phosphorylation	KLFPKSDSKALDLLD HHCCCCCHHHHHHHH	27.24	-
303	Acetylation	LFPKSDSKALDLLDR HCCCCCHHHHHHHHH	58.94	22902405

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	MAP2K1	Q02750	GPS
203	T	Phosphorylation	Kinase	MEK1	Q01986	PSP
203	T	Phosphorylation	Kinase	MAP2K2	P36506	Uniprot
205	Y	Phosphorylation	Kinase	MAP2K1	Q02750	GPS
205	Y	Phosphorylation	Kinase	MEK1	Q01986	PSP
205	Y	Phosphorylation	Kinase	MAP2K2	P36506	Uniprot
208	T	Phosphorylation	Kinase	MAPK3	P21708	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	Map3k1	Q62925	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
203	T	Phosphorylation	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.

Oops, there are no SNP-PTM records of MK03_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
MK01_RAT	Mapk1	physical	20181831
CNN3_RAT	Cnn3	physical	20181831
PGH2_RAT	Ptgs2	physical	17984113

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"Quantitative phosphoproteomics of vasopressin-sensitive renal cells:regulation of aquaporin-2 phosphorylation at two sites.";
Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-203 AND TYR-205, ANDMASS SPECTROMETRY.
PubMed: 16641100