MAPK5_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: MAPK5_MOUSE
• UniProt AC: O54992
• Protein Name: MAP kinase-activated protein kinase 5
• Gene Name: Mapkapk5
• Organism: Mus musculus (Mouse).
• Sequence Length: 473
• Subcellular Localization: Cytoplasm. Nucleus. Translocates to the cytoplasm following phosphorylation and activation. Interaction with ERK3/MAPK6 or ERK4/MAPK4 and phosphorylation at Thr-182, activates the protein kinase activity, followed by translocation to the cytoplasm. P
• Protein Description: Tumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation. Phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. Acts as a tumor suppressor by mediating Ras-induced senescence and phosphorylating p53/TP53. Involved in post-transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3, enabling expression of miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. Part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation, inducing F-actin rearrangement..
• Protein Sequence: MSEDSDMEKAIKETSILEEYSINWTQKLGAGISGPVRVCVKKSTQERFALKILLDRPKARNEVRLHMMCATHPNIVQIIEVFANSVQFPHESSPRARLLIVMEMMEGGELFHRISQHRHFTEKQASQVTKQIALALQHCHLLNIAHRDLKPENLLFKDNSLDAPVKLCDFGFAKVDQGDLMTPQFTPYYVAPQVLEAQRRHQKEKSGIIPTSPTPYTYNKSCDLWSLGVIIYVMLCGYPPFYSKHHSRTIPKDMRKKIMTGSFEFPEEEWSQISEMAKDVVRKLLKVKPEERLTIEGVLDHPWLNSTEALDNVLPSAQLMMDKAVVAGIQQAHAEQLANMRIQDLKVSLKPLHSVNNPILRKRKLLGTKPKDGIYIHDHENGTEDSNVALEKLRDVIAQCILPQAGKGENEDEKLNEVMQEAWKYNRECKLLRDALQSFSWNGRGFTDKVDRLKLAEVVKQVIEEQTLPHEPQ

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	Phosphorylation	------MSEDSDMEK ------CCCHHHHHH	50.54	27087446
5	Phosphorylation	---MSEDSDMEKAIK ---CCCHHHHHHHHH	34.50	27087446
51	Acetylation	TQERFALKILLDRPK HHHHHHHHHHHCCHH	28.07	56141211
115	Phosphorylation	GELFHRISQHRHFTE CHHHHHHHHCCCCCH	21.64	20734105
182	Phosphorylation	VDQGDLMTPQFTPYY CCCCCCCCCCCCCCC	22.64	26824392
186	Phosphorylation	DLMTPQFTPYYVAPQ CCCCCCCCCCCCCHH	12.72	23984901
188	Phosphorylation	MTPQFTPYYVAPQVL CCCCCCCCCCCHHHH	13.91	23984901
189	Phosphorylation	TPQFTPYYVAPQVLE CCCCCCCCCCHHHHH	7.43	23984901
211	Phosphorylation	EKSGIIPTSPTPYTY HHCCCCCCCCCCCCC	36.61	26643407
212	Phosphorylation	KSGIIPTSPTPYTYN HCCCCCCCCCCCCCC	22.79	26745281
214	Phosphorylation	GIIPTSPTPYTYNKS CCCCCCCCCCCCCCC	28.79	26745281
216	Phosphorylation	IPTSPTPYTYNKSCD CCCCCCCCCCCCCCC	25.08	26643407
354	Phosphorylation	VSLKPLHSVNNPILR CCCCCCCCCCCHHHH	33.93	26824392
364	Acetylation	NPILRKRKLLGTKPK CHHHHHHHCCCCCCC	51.61	56141209
368	Phosphorylation	RKRKLLGTKPKDGIY HHHHCCCCCCCCCEE	44.11	25367039

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
115	S	Phosphorylation	Kinase	PKA-FAMILY	-	GPS
115	S	Phosphorylation	Kinase	PKA	-	Uniprot
182	T	Phosphorylation	Kinase	MAPK4	Q6P5G0	Uniprot
182	T	Phosphorylation	Kinase	MAPK6	Q61532	Uniprot
182	T	Phosphorylation	Kinase	P38B	Q9WUI1	PSP
182	T	Phosphorylation	Kinase	MAPK14	P47811	Uniprot
182	T	Phosphorylation	Kinase	PKA-FAMILY	-	GPS
182	T	Phosphorylation	Kinase	PKA	-	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
115	S	Phosphorylation	Phosphorylated at Ser-115 by PKA/PRKACA, leading to localization to the cytoplasm.	20734105
182	T	Phosphorylation	Phosphorylated on Thr-182 ERK3/MAPK6 or ERK4/MAPK4; which is the regulatory phosphorylation site and is located on the T-loop/loop 12, leading to activation.	15538386
182	T	Phosphorylation	Phosphorylation at Thr-182 by p38-alpha/MAPK14, p38-beta/MAPK11 is subject to debate.	15538386

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of MAPK5_MOUSE !!

Protein-Protein Interaction

Oops, there are no PPI records of MAPK5_MOUSE !!

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"Serine residue 115 of MAPK-activated protein kinase MK5 is crucialfor its PKA-regulated nuclear export and biological function.";
Kostenko S., Shiryaev A., Gerits N., Dumitriu G., Klenow H.,Johannessen M., Moens U.;
Cell. Mol. Life Sci. 68:847-862(2011).
Cited for: PHOSPHORYLATION AT SER-115, SUBCELLULAR LOCATION, AND MUTAGENESIS OFSER-115.
PubMed: 20734105

"Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines anovel signal transduction pathway.";
Seternes O.M., Mikalsen T., Johansen B., Michaelsen E.,Armstrong C.G., Morrice N.A., Turgeon B., Meloche S., Moens U.,Keyse S.M.;
EMBO J. 23:4780-4791(2004).
Cited for: FUNCTION IN PHOSPHORYLATION OF MAPK6, SUBCELLULAR LOCATION,INTERACTION WITH MAPK6, PHOSPHORYLATION AT THR-182, AND MUTAGENESIS OFTHR-182.
PubMed: 15577943

"Scaffolding by ERK3 regulates MK5 in development.";
Schumacher S., Laass K., Kant S., Shi Y., Visel A., Gruber A.D.,Kotlyarov A., Gaestel M.;
EMBO J. 23:4770-4779(2004).
Cited for: FUNCTION IN PHOSPHORYLATION OF MAPK6, SUBCELLULAR LOCATION,INTERACTION WITH MAPK6, AUTOPHOSPHORYLATION, PHOSPHORYLATION ATTHR-182, MUTAGENESIS OF LYS-51 AND THR-182, AND DISRUPTION PHENOTYPE.
PubMed: 15538386