dbPTM

MK01_RAT - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MK01_RAT
UniProt AC	P63086
Protein Name	Mitogen-activated protein kinase 1
Gene Name	Mapk1
Organism	Rattus norvegicus (Rat).
Sequence Length	358
Subcellular Localization	Cytoplasm, cytoskeleton, spindle. Nucleus. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm . Membrane, caveola . Associated with the spindle during prometaphase and metaphase. PEA15-binding and phosphorylated DAPK1 promo
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, DCC, 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. Mediates phosphorylation of TPR in respons to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation (By similarity). Phosphorylates CDK2AP2. [PubMed: 12944431; Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.]
Protein Sequence	MAAAAAAGPEMVRGQVFDVGPRYTNLSYIGEGAYGMVCSAYDNLNKVRVAIKKISPFEHQTYCQRTLREIKILLRFRHENIIGINDIIRAPTIEQMKDVYIVQDLMETDLYKLLKTQHLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTTCDLKICDFGLARVADPDHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINLKARNYLLSLPHKNKVPWNRLFPNADSKALDLLDKMLTFNPHKRIEVEQALAHPYLEQYYDPSDEPIAEAPFKFDMELDDLPKEKLKELIFEETARFQPGYRS

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MAAAAAAGP ------CCHHHHCCH	13.05	-
27	Phosphorylation	GPRYTNLSYIGEGAY CCCCCCCEEECCCCH	19.44	-
28	Phosphorylation	PRYTNLSYIGEGAYG CCCCCCEEECCCCHH	18.99	-
41	Phosphorylation	YGMVCSAYDNLNKVR HHHHHHHHHCCCCEE	6.78	-
136	Acetylation	YQILRGLKYIHSANV HHHHHHCHHHHHCCC	45.01	-
164	S-nitrosylation	TTCDLKICDFGLARV CCCCEEECCCCCEEE	3.20	21278135
164	S-nitrosocysteine	TTCDLKICDFGLARV CCCCEEECCCCCEEE	3.20	-
179	Phosphorylation	ADPDHDHTGFLTEYV CCCCCCCCCHHHHHH	35.37	27097102
183	Phosphorylation	HDHTGFLTEYVATRW CCCCCHHHHHHHHCC	24.02	22609512
185	Phosphorylation	HTGFLTEYVATRWYR CCCHHHHHHHHCCCC	7.08	28689409
188	Phosphorylation	FLTEYVATRWYRAPE HHHHHHHHCCCCCCE	16.22	27097102
203	Phosphorylation	IMLNSKGYTKSIDIW EHHCCCCCCCCHHHH	18.09	-
204	Phosphorylation	MLNSKGYTKSIDIWS HHCCCCCCCCHHHHH	27.30	-
244	Phosphorylation	HILGILGSPSQEDLN HHHHHCCCCCHHHHH	20.24	-
246	Phosphorylation	LGILGSPSQEDLNCI HHHCCCCCHHHHHHH	48.15	-
268	Acetylation	YLLSLPHKNKVPWNR HHHHCCCCCCCCHHH	57.43	22902405
282	Phosphorylation	RLFPNADSKALDLLD HCCCCCCHHHHHHHH	19.88	-
283	Acetylation	LFPNADSKALDLLDK CCCCCCHHHHHHHHH	54.22	22902405
290	Acetylation	KALDLLDKMLTFNPH HHHHHHHHHHHCCHH	35.46	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
27	S	Phosphorylation	Kinase	SGK1	Q06226	Uniprot
183	T	Phosphorylation	Kinase	MAPK1	P63086	GPS
183	T	Phosphorylation	Kinase	MEK1	Q02750	PSP
183	T	Phosphorylation	Kinase	MAP2K1	P29678	GPS
183	T	Phosphorylation	Kinase	MEK1	Q01986	PSP
185	Y	Phosphorylation	Kinase	MAPK1	P63086	GPS
185	Y	Phosphorylation	Kinase	MAP2K1	Q02750	GPS
185	Y	Phosphorylation	Kinase	MEK1	Q01986	PSP
188	T	Phosphorylation	Kinase	ERK2	P28482	PSP
188	T	Phosphorylation	Kinase	MAPK1	P63086	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	Map3k1	Q62925	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
27	S	Phosphorylation	-
Phosphorylation on Ser-27 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2 (By similarity).
183	T	Phosphorylation	22673903
Dephosphorylated by DUSP1 at Thr-183 and Tyr-185.
183	T	Phosphorylation	22673903
Dually phosphorylated on Thr-183 and Tyr-185, 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 MK01_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
HIF1A_HUMAN	HIF1A	physical	10551817
PARP1_HUMAN	PARP1	physical	17244536
MK03_RAT	Mapk3	physical	20181831
CNN3_RAT	Cnn3	physical	20181831
SCNNB_RAT	Scnn1b	physical	11805112
SCNNG_RAT	Scnn1g	physical	11805112
MBP_RAT	Mbp	physical	9722539
PGH2_RAT	Ptgs2	physical	17984113
TNR1A_MOUSE	Tnfrsf1a	physical	15865443

Drug and Disease Associations

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

Regulatory Network of MK01_RAT

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"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-183; TYR-185 ANDTHR-188, AND MASS SPECTROMETRY.	16641100 [Abstract]

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