dbPTM

MAPK5_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MAPK5_HUMAN
UniProt AC	Q8IW41
Protein Name	MAP kinase-activated protein kinase 5
Gene Name	MAPKAPK5
Organism	Homo sapiens (Human).
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	MSEESDMDKAIKETSILEEYSINWTQKLGAGISGPVRVCVKKSTQERFALKILLDRPKARNEVRLHMMCATHPNIVQIIEVFANSVQFPHESSPRARLLIVMEMMEGGELFHRISQHRHFTEKQASQVTKQIALALRHCHLLNIAHRDLKPENLLFKDNSLDAPVKLCDFGFAKIDQGDLMTPQFTPYYVAPQVLEAQRRHQKEKSGIIPTSPTPYTYNKSCDLWSLGVIIYVMLCGYPPFYSKHHSRTIPKDMRRKIMTGSFEFPEEEWSQISEMAKDVVRKLLKVKPEERLTIEGVLDHPWLNSTEALDNVLPSAQLMMDKAVVAGIQQAHAEQLANMRIQDLKVSLKPLHSVNNPILRKRKLLGTKPKDSVYIHDHENGAEDSNVALEKLRDVIAQCILPQAGKGENEDEKLNEVMQEAWKYNRECKLLRDTLQSFSWNGRGFTDKVDRLKLAEIVKQVIEEQTTSHESQ

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
57	Ubiquitination	LKILLDRPKARNEVR HHHHHCCHHHHCHHH	34.03	22817900
81	Ubiquitination	NIVQIIEVFANSVQF CHHHHHHHHHHHCCC	3.75	22817900
84	Ubiquitination	QIIEVFANSVQFPHE HHHHHHHHHCCCCCC	31.11	22817900
93	Phosphorylation	VQFPHESSPRARLLI CCCCCCCCHHHHEEE	18.54	-
115	Phosphorylation	GELFHRISQHRHFTE CHHHHHHHHCCCCCH	21.64	20734105
123	Ubiquitination	QHRHFTEKQASQVTK HCCCCCHHHHHHHHH	48.37	-
150	Ubiquitination	NIAHRDLKPENLLFK HHHCCCCCHHHCCCC	55.35	22817900
166	Ubiquitination	NSLDAPVKLCDFGFA CCCCCCEEECCCCCE	42.19	29967540
182	Phosphorylation	IDQGDLMTPQFTPYY CCCCCCCCCCCCCEE	22.64	20734105
186	Phosphorylation	DLMTPQFTPYYVAPQ CCCCCCCCCEECCHH	12.72	28450419
188	Phosphorylation	MTPQFTPYYVAPQVL CCCCCCCEECCHHHH	13.91	26074081
189	Phosphorylation	TPQFTPYYVAPQVLE CCCCCCEECCHHHHH	7.43	26074081
205	Ubiquitination	QRRHQKEKSGIIPTS HHHHHHHHCCCCCCC	62.10	29967540
206	Phosphorylation	RRHQKEKSGIIPTSP HHHHHHHCCCCCCCC	35.99	-
211	Phosphorylation	EKSGIIPTSPTPYTY HHCCCCCCCCCCCCC	36.61	25159151
212	Phosphorylation	KSGIIPTSPTPYTYN HCCCCCCCCCCCCCC	22.79	25159151
214	Phosphorylation	GIIPTSPTPYTYNKS CCCCCCCCCCCCCCC	28.79	28985074
216	Phosphorylation	IPTSPTPYTYNKSCD CCCCCCCCCCCCCCC	25.08	27732954
217	Phosphorylation	PTSPTPYTYNKSCDL CCCCCCCCCCCCCCH	23.09	27732954
218	Phosphorylation	TSPTPYTYNKSCDLW CCCCCCCCCCCCCHH	18.10	27732954
286	Ubiquitination	DVVRKLLKVKPEERL HHHHHHHCCCHHHCC	59.66	29967540
348	Phosphorylation	RIQDLKVSLKPLHSV CHHHHCCCCCCCCCC	29.14	20873877
354	Phosphorylation	VSLKPLHSVNNPILR CCCCCCCCCCCHHHH	33.93	29255136
368	Phosphorylation	RKRKLLGTKPKDSVY HHHHHCCCCCCCCEE	44.11	28188228
467	Phosphorylation	KQVIEEQTTSHESQ- HHHHHHHHCCCCCC-	33.28	22115753
468	Phosphorylation	QVIEEQTTSHESQ-- HHHHHHHCCCCCC--	27.99	22617229
469	Phosphorylation	VIEEQTTSHESQ--- HHHHHHCCCCCC---	28.75	25159151
470	Phosphorylation	IEEQTTSHESQ---- HHHHHCCCCCC----	36.31	33259812
472	Phosphorylation	EQTTSHESQ------ HHHCCCCCC------	35.45	25159151

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	PRKACA	P17612	GPS
115	S	Phosphorylation	Kinase	PKA	-	Uniprot
182	T	Phosphorylation	Kinase	MAPK1	P28482	GPS
182	T	Phosphorylation	Kinase	MAPK4	P31152	Uniprot
182	T	Phosphorylation	Kinase	MAPK6	Q16659	Uniprot
182	T	Phosphorylation	Kinase	MAPK9	P45984	GPS
182	T	Phosphorylation	Kinase	MK11	Q15759	PhosphoELM
182	T	Phosphorylation	Kinase	MK14	Q16539	PhosphoELM
182	T	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS
182	T	Phosphorylation	Kinase	PKA-FAMILY	-	GPS
182	T	Phosphorylation	Kinase	PKA	-	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
115	S	Phosphorylation	-
Phosphorylated at Ser-115 by PKA/PRKACA, leading to localization to the cytoplasm.
182	T	Phosphorylation	9628874
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.
182	T	Phosphorylation	9628874
Phosphorylation at Thr-182 by p38-alpha/MAPK14, p38-beta/MAPK11 is subject to debate.

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 MAPK5_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
HSPB1_HUMAN	HSPB1	physical	9628874
HSPB2_HUMAN	HSPB2	physical	9628874
RL13_HUMAN	RPL13	physical	21900206
ZN282_HUMAN	ZNF282	physical	21900206
MK04_HUMAN	MAPK4	physical	21675959
MAPK2_HUMAN	MAPKAPK2	physical	21675959
ZN576_HUMAN	ZNF576	physical	21988832
P53_HUMAN	TP53	physical	17254968
MK09_HUMAN	MAPK9	physical	25241761
MK01_HUMAN	MAPK1	physical	25241761
4EBP1_HUMAN	EIF4EBP1	physical	25241761
HSPB1_HUMAN	HSPB1	physical	19166925
MAPK5_HUMAN	MAPKAPK5	physical	19166925
HSPB1_HUMAN	HSPB1	physical	10978313

Drug and Disease Associations

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

Regulatory Network of MAPK5_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions."; Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.; Sci. Signal. 2:RA46-RA46(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-182 AND SER-472, ANDMASS SPECTROMETRY.	19690332 [Abstract]
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach."; Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.; Anal. Chem. 81:4493-4501(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-214 AND SER-472, ANDMASS SPECTROMETRY.	19413330 [Abstract]
"Regulation of PRAK subcellular location by p38 MAP kinases."; New L., Jiang Y., Han J.; Mol. Biol. Cell 14:2603-2616(2003). Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-212, MUTAGENESIS OFTHR-182, AND MUTAGENESIS OF LYS-51; THR-182 AND SER-212.	12808055 [Abstract]
"A quantitative atlas of mitotic phosphorylation."; Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-182, AND MASSSPECTROMETRY.	18669648 [Abstract]
"PRAK, a novel protein kinase regulated by the p38 MAP kinase."; New L., Jiang Y., Zhao M., Liu K., Zhu W., Flood L.J., Kato Y.,Parry G.C.N., Han J.; EMBO J. 17:3372-3384(1998). Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2), MUTAGENESIS OF THR-182,FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION AT THR-182, AND ENZYMEREGULATION.	9628874 [Abstract]

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