dbPTM

MAPK2_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MAPK2_MOUSE
UniProt AC	P49138
Protein Name	MAP kinase-activated protein kinase 2
Gene Name	Mapkapk2
Organism	Mus musculus (Mouse).
Sequence Length	386
Subcellular Localization	Cytoplasm. Nucleus. Phosphorylation and subsequent activation releases the autoinhibitory helix, resulting in the export from the nucleus into the cytoplasm.
Protein Description	Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities (By similarity). Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress following ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites (By similarity). Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3..
Protein Sequence	MLSGSPGQTPPAPFPSPPPPAPAQPPPPFPQFHVKSGLQIRKNAITDDYKVTSQVLGLGINGKVLRIFDKRTQQKFALKMLQDCPKARREVELHWRASQCPHIVHIVDVYENLYAGRKCLLIVMECLDGGELFSRIQDRGDQAFTEREASEIMKSIGEAIQYLHSINIAHRDVKPENLLYTSKRPNAILKLTDFGFAKETTSHNSLTTPCYTPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGYPPFYSNHGLAISPGMKTRIRMGQYEFPNPEWSEVSEEVKMLIRNLLKTEPTQRMTITEFMNHPWIMQSTKVPQTPLHTSRVLKEDKERWEDVKEEMTSALATMRVDYEQIKIKKIEDASNPLLLKRRKKARAVEDAALAH

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
3	Phosphorylation	-----MLSGSPGQTP -----CCCCCCCCCC	35.61	26745281
5	Phosphorylation	---MLSGSPGQTPPA ---CCCCCCCCCCCC	23.60	26745281
9	Phosphorylation	LSGSPGQTPPAPFPS CCCCCCCCCCCCCCC	36.84	26745281
16	Phosphorylation	TPPAPFPSPPPPAPA CCCCCCCCCCCCCCC	50.87	26745281
50	Acetylation	NAITDDYKVTSQVLG CCCCCCCCHHHHHCC	46.13	22902405
53	Phosphorylation	TDDYKVTSQVLGLGI CCCCCHHHHHCCCCC	22.68	27180971
75	Malonylation	FDKRTQQKFALKMLQ ECHHHHHHHHHHHHH	23.84	26320211
75	Acetylation	FDKRTQQKFALKMLQ ECHHHHHHHHHHHHH	23.84	22826441
84	Glutathionylation	ALKMLQDCPKARREV HHHHHHHCHHHHHHH	2.10	24333276
200	Phosphorylation	DFGFAKETTSHNSLT CCCCCCCCCCCCCCC	32.65	23984901
201	Phosphorylation	FGFAKETTSHNSLTT CCCCCCCCCCCCCCC	29.13	23984901
202	Phosphorylation	GFAKETTSHNSLTTP CCCCCCCCCCCCCCC	28.26	24719451
205	Phosphorylation	KETTSHNSLTTPCYT CCCCCCCCCCCCCCC	22.97	29472430
207	Phosphorylation	TTSHNSLTTPCYTPY CCCCCCCCCCCCCCC	28.63	19060867
208	Phosphorylation	TSHNSLTTPCYTPYY CCCCCCCCCCCCCCE	19.36	22322096
211	Phosphorylation	NSLTTPCYTPYYVAP CCCCCCCCCCCEECH	16.38	23984901
212	Phosphorylation	SLTTPCYTPYYVAPE CCCCCCCCCCEECHH	16.13	29472430
214	Phosphorylation	TTPCYTPYYVAPEVL CCCCCCCCEECHHHH	11.63	29514104
215	Phosphorylation	TPCYTPYYVAPEVLG CCCCCCCEECHHHHC	7.43	29472430
258	Phosphorylation	SNHGLAISPGMKTRI CCCCCEECCCCCCEE	15.14	-
303	Phosphorylation	PTQRMTITEFMNHPW CCCCCCHHHHHCCCH	17.63	22322096
314	Phosphorylation	NHPWIMQSTKVPQTP CCCHHHCCCCCCCCC	16.89	22322096
320	Phosphorylation	QSTKVPQTPLHTSRV CCCCCCCCCCCHHHH	23.03	22322096
324	Phosphorylation	VPQTPLHTSRVLKED CCCCCCCHHHHHHHH	26.38	22322096
325	Phosphorylation	PQTPLHTSRVLKEDK CCCCCCHHHHHHHHH	15.05	22322096
329	Acetylation	LHTSRVLKEDKERWE CCHHHHHHHHHHHHH	62.09	6569173
339	Sumoylation	KERWEDVKEEMTSAL HHHHHHHHHHHHHHH	61.35	-
353	Phosphorylation	LATMRVDYEQIKIKK HHHCCCCHHHHEEEE	13.58	25159016

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
208	T	Phosphorylation	Kinase	MAPK3	Q63844	GPS
208	T	Phosphorylation	Kinase	MAPK14	P47811	Uniprot
258	S	Phosphorylation	Kinase	MAPK14	P47811	Uniprot
320	T	Phosphorylation	Kinase	MAPK1	P63085	GPS
320	T	Phosphorylation	Kinase	MAPK3	Q63844	GPS
320	T	Phosphorylation	Kinase	MAPK14	P47811	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
208	T	Phosphorylation	7592979
Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-208; Ser-258 and Thr-320.
258	S	Phosphorylation	7592979
Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-208; Ser-258 and Thr-320.
320	T	Phosphorylation	7592979
Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-208; Ser-258 and Thr-320.

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 MAPK2_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
PHC2_MOUSE	Phc2	physical	19369945
PHC1_MOUSE	Phc1	physical	19369945
MK14_MOUSE	Mapk14	physical	19369945
RING2_MOUSE	Rnf2	physical	19369945
LSP1_MOUSE	Lsp1	physical	17481585
ROA0_MOUSE	Hnrnpa0	physical	12456657
HSPB1_MOUSE	Hspb1	physical	14578350

Drug and Disease Associations

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

Regulatory Network of MAPK2_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"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 THR-208; THR-320 ANDTHR-324, AND MASS SPECTROMETRY.	17242355 [Abstract]
"Leptomycin B-sensitive nuclear export of MAPKAP kinase 2 is regulatedby phosphorylation."; Engel K., Kotlyarov A., Gaestel M.; EMBO J. 17:3363-3371(1998). Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-208 AND THR-320, ANDNUCLEAR EXPORT SIGNAL (NES).	9628873 [Abstract]
"Constitutive activation of mitogen-activated protein kinase-activatedprotein kinase 2 by mutation of phosphorylation sites and an A-helixmotif."; Engel K., Schultz H., Martin F., Kotlyarov A., Plath K., Hahn M.,Heinemann U., Gaestel M.; J. Biol. Chem. 270:27213-27221(1995). Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-208 AND THR-320, ANDMUTAGENESIS OF THR-208; THR-320; LYS-329 AND TRP-335.	7592979 [Abstract]

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