MP2K4_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: MP2K4_MOUSE
• UniProt AC: P47809
• Protein Name: Dual specificity mitogen-activated protein kinase kinase 4
• Gene Name: Map2k4
• Organism: Mus musculus (Mouse).
• Sequence Length: 397
• Subcellular Localization: Cytoplasm . Nucleus .
• Protein Description: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14..
• Protein Sequence: MAAPSPSGGGGSGGGGGTPGPIGPPASGHPAVSSMQGKRKALKLNFANPPVKSTARFTLNPNTTGVQNPHIERLRTHSIESSGKLKISPEQHWDFTAEDLKDLGEIGRGAYGSVNKMVHKPSGQIMAVKRIRSTVDEKEQKQLLMDLDVVMRSSDCPYIVQFYGALFREGDCWICMELMSTSFDKFYKYVYSVLDDVIPEEILGKITLATVKALNHLKENLKIIHRDIKPSNILLDRSGNIKLCDFGISGQLVDSIAKTRDAGCRPYMAPERIDPSASRQGYDVRSDVWSLGITLYELATGRFPYPKWNSVFDQLTQVVKGDPPQLSNSEEREFSPSFINFVNLCLTKDESKRPKYKELLKHPFILMYEERTVEVACYVCKILDQMPATPSSPMYVD

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	------MAAPSPSGG ------CCCCCCCCC	28.25	-
5	Phosphorylation	---MAAPSPSGGGGS ---CCCCCCCCCCCC	27.29	30482847
52	Ubiquitination	NFANPPVKSTARFTL CCCCCCCCCCEEEEE	48.11	22790023
54	Phosphorylation	ANPPVKSTARFTLNP CCCCCCCCEEEEECC	19.01	-
56	Asymmetric dimethylarginine	PPVKSTARFTLNPNT CCCCCCEEEEECCCC	25.77	-
56	Methylation	PPVKSTARFTLNPNT CCCCCCEEEEECCCC	25.77	24129315
76	Phosphorylation	PHIERLRTHSIESSG CCHHHHHHCEECCCC	25.27	22324799
78	Phosphorylation	IERLRTHSIESSGKL HHHHHHCEECCCCCC	27.69	26824392
81	Phosphorylation	LRTHSIESSGKLKIS HHHCEECCCCCCCCC	42.60	25266776
82	Phosphorylation	RTHSIESSGKLKISP HHCEECCCCCCCCCH	27.44	26745281
88	Phosphorylation	SSGKLKISPEQHWDF CCCCCCCCHHHHCCC	22.31	25521595
96	Phosphorylation	PEQHWDFTAEDLKDL HHHHCCCCHHHHHHH	27.02	24925903
101	Acetylation	DFTAEDLKDLGEIGR CCCHHHHHHHHHHCC	64.33	23954790
218	Acetylation	VKALNHLKENLKIIH HHHHHHHHHHHEEEC	36.69	23954790
244	S-nitrosocysteine	RSGNIKLCDFGISGQ CCCCEEECCCCCCHH	3.28	-
244	S-nitrosylation	RSGNIKLCDFGISGQ CCCCEEECCCCCCHH	3.28	16418269
255	Phosphorylation	ISGQLVDSIAKTRDA CCHHHHHHHHHHCCC	19.57	22322096
259	Phosphorylation	LVDSIAKTRDAGCRP HHHHHHHHCCCCCCC	25.43	22322096
264	Glutathionylation	AKTRDAGCRPYMAPE HHHCCCCCCCCCCCC	4.20	24333276
276	Phosphorylation	APERIDPSASRQGYD CCCCCCCCHHHCCCC	34.82	25521595
278	Phosphorylation	ERIDPSASRQGYDVR CCCCCCHHHCCCCCH	29.49	25521595
294	Phosphorylation	DVWSLGITLYELATG HHHHHCCCHHHHHHC	22.84	28576409
389	Phosphorylation	ILDQMPATPSSPMYV HHHCCCCCCCCCCCC	20.17	25521595
391	Phosphorylation	DQMPATPSSPMYVD- HCCCCCCCCCCCCC-	42.60	25521595
392	Phosphorylation	QMPATPSSPMYVD-- CCCCCCCCCCCCC--	18.19	25521595
395	Phosphorylation	ATPSSPMYVD----- CCCCCCCCCC-----	12.59	25521595

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
78	S	Phosphorylation	Kinase	AKT1	P31750	PSP
78	S	Phosphorylation	Kinase	SGK1	Q9WVC6	PSP
78	S	Phosphorylation	Kinase	SGK1	Q06226	PSP
78	S	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
255	S	Phosphorylation	Kinase	MAP3K11	Q16584	GPS
255	S	Phosphorylation	Kinase	MAP3K12	Q60700	GPS
259	T	Phosphorylation	Kinase	MAP3K11	Q16584	GPS
259	T	Phosphorylation	Kinase	MAP3K12	Q60700	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
255	S	Phosphorylation	Activated by phosphorylation on Ser-255 and Thr-259 by MAP kinase kinase kinases (MAP3Ks).	21183079
259	T	Phosphorylation	Activated by phosphorylation on Ser-255 and Thr-259 by MAP kinase kinase kinases (MAP3Ks).	21183079

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of MP2K4_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
MK10_MOUSE	Mapk10	physical	15218018

Drug and Disease Associations

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