dbPTM

MAPK3_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MAPK3_HUMAN
UniProt AC	Q16644
Protein Name	MAP kinase-activated protein kinase 3
Gene Name	MAPKAPK3
Organism	Homo sapiens (Human).
Sequence Length	382
Subcellular Localization	Nucleus . Cytoplasm . Predominantly located in the nucleus, when activated it translocates to the cytoplasm.
Protein Description	Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling 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. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair 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, such as TTP/ZFP36, leading to regulate 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 transcript. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression..
Protein Sequence	MDGETAEEQGGPVPPPVAPGGPGLGGAPGGRREPKKYAVTDDYQLSKQVLGLGVNGKVLECFHRRTGQKCALKLLYDSPKARQEVDHHWQASGGPHIVCILDVYENMHHGKRCLLIIMECMEGGELFSRIQERGDQAFTEREAAEIMRDIGTAIQFLHSHNIAHRDVKPENLLYTSKEKDAVLKLTDFGFAKETTQNALQTPCYTPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGFPPFYSNTGQAISPGMKRRIRLGQYGFPNPEWSEVSEDAKQLIRLLLKTDPTERLTITQFMNHPWINQSMVVPQTPLHTARVLQEDKDHWDEVKEEMTSALATMRVDYDQVKIKDLKTSNNRLLNKRRKKQAGSSSASQGCNNQ

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
1	Acetylation	-------MDGETAEE -------CCCCCHHH	15.67	22814378
5	Phosphorylation	---MDGETAEEQGGP ---CCCCCHHHCCCC	44.92	-
36	Ubiquitination	GGRREPKKYAVTDDY CCCCCCCCEEECCCH	49.51	-
43	Phosphorylation	KYAVTDDYQLSKQVL CEEECCCHHHHHHHH	17.73	27642862
47	Ubiquitination	TDDYQLSKQVLGLGV CCCHHHHHHHHCCCC	53.68	-
73	Acetylation	TGQKCALKLLYDSPK HCCHHHHHHHHCCHH	20.23	25953088
76	Phosphorylation	KCALKLLYDSPKARQ HHHHHHHHCCHHHHH	25.47	25147952
78	Phosphorylation	ALKLLYDSPKARQEV HHHHHHCCHHHHHHC	18.10	23186163
80	Ubiquitination	KLLYDSPKARQEVDH HHHHCCHHHHHHCHH	61.22	-
139	Phosphorylation	ERGDQAFTEREAAEI HHCCHHCCHHHHHHH	36.83	26546556
168	Ubiquitination	NIAHRDVKPENLLYT CCCCCCCCHHHCEEC	51.40	-
177	Acetylation	ENLLYTSKEKDAVLK HHCEECCCCCCCEEH	62.07	155663
179	Acetylation	LLYTSKEKDAVLKLT CEECCCCCCCEEHHH	55.51	7483973
184	Ubiquitination	KEKDAVLKLTDFGFA CCCCCEEHHHCCCCC	42.62	-
192	Ubiquitination	LTDFGFAKETTQNAL HHCCCCCHHHHHCHH	54.02	-
194	Phosphorylation	DFGFAKETTQNALQT CCCCCHHHHHCHHCC	32.73	28450419
195	Phosphorylation	FGFAKETTQNALQTP CCCCHHHHHCHHCCC	22.40	21945579
201	Phosphorylation	TTQNALQTPCYTPYY HHHCHHCCCCCCCCC	19.04	21945579
204	Phosphorylation	NALQTPCYTPYYVAP CHHCCCCCCCCCCCH	16.38	21945579
205	Phosphorylation	ALQTPCYTPYYVAPE HHCCCCCCCCCCCHH	16.13	21945579
207	Phosphorylation	QTPCYTPYYVAPEVL CCCCCCCCCCCHHHH	11.63	21945579
208	Phosphorylation	TPCYTPYYVAPEVLG CCCCCCCCCCHHHHC	7.43	21945579
219	Phosphorylation	EVLGPEKYDKSCDMW HHHCCHHCCCCCHHH	27.26	23312004
244	Phosphorylation	CGFPPFYSNTGQAIS HCCCCCCCCCCCCCC	28.44	20058876
246	Phosphorylation	FPPFYSNTGQAISPG CCCCCCCCCCCCCCC	25.40	20058876
251	Phosphorylation	SNTGQAISPGMKRRI CCCCCCCCCCCCHHE	20.58	20058876
286	Ubiquitination	QLIRLLLKTDPTERL HHHHHHHHCCCCCCE	51.34	-
286	Acetylation	QLIRLLLKTDPTERL HHHHHHHHCCCCCCE	51.34	25953088
307	Phosphorylation	NHPWINQSMVVPQTP CCCCCCCCCEECCCC	14.73	22322096
313	Phosphorylation	QSMVVPQTPLHTARV CCCEECCCCCHHHHH	23.03	22322096
317	Phosphorylation	VPQTPLHTARVLQED ECCCCCHHHHHHHHC	24.68	22322096
325	Ubiquitination	ARVLQEDKDHWDEVK HHHHHHCHHCHHHHH	51.22	-
332	Ubiquitination	KDHWDEVKEEMTSAL HHCHHHHHHHHHHHH	46.00	-
332	Acetylation	KDHWDEVKEEMTSAL HHCHHHHHHHHHHHH	46.00	7432005
337	Phosphorylation	EVKEEMTSALATMRV HHHHHHHHHHHHHCC	21.70	28555341
346	Phosphorylation	LATMRVDYDQVKIKD HHHHCCCHHHHHHHH	12.86	28796482
350	Ubiquitination	RVDYDQVKIKDLKTS CCCHHHHHHHHCHHC	38.10	-
372	Phosphorylation	RRKKQAGSSSASQGC HHHHHCCCCHHHCCC	24.92	22210691
373	Phosphorylation	RKKQAGSSSASQGCN HHHHCCCCHHHCCCC	29.07	-
374	Phosphorylation	KKQAGSSSASQGCNN HHHCCCCHHHCCCCC	33.37	-
376	Phosphorylation	QAGSSSASQGCNNQ- HCCCCHHHCCCCCC-	29.11	22210691

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
201	T	Phosphorylation	Kinase	MAPK14	Q16539	Uniprot
251	S	Phosphorylation	Kinase	MAPK14	Q16539	Uniprot
313	T	Phosphorylation	Kinase	MAPK14	Q16539	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
201	T	Phosphorylation	-
Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-201, Ser-251 and Thr-313 (By similarity).
251	S	Phosphorylation	-
Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-201, Ser-251 and Thr-313 (By similarity).
313	T	Phosphorylation	-
Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-201, Ser-251 and Thr-313 (By similarity).

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 MAPK3_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
MK14_HUMAN	MAPK14	physical	11157753
TFE2_HUMAN	TCF3	physical	10781029
RAB2A_HUMAN	RAB2A	physical	21900206
SUMO3_HUMAN	SUMO3	physical	21900206
CSN6_HUMAN	COPS6	physical	21900206
SPSY_HUMAN	SMS	physical	21900206
EZH2_HUMAN	EZH2	physical	21900206
PHC2_HUMAN	PHC2	physical	15563468
BMI1_HUMAN	BMI1	physical	15563468
A4_HUMAN	APP	physical	21832049
HSPB1_HUMAN	HSPB1	physical	8774846
MK11_HUMAN	MAPK11	physical	26186194
ATF1_HUMAN	ATF1	physical	11335727
CPZIP_HUMAN	RCSD1	physical	15850461
BECN1_HUMAN	BECN1	physical	25693418
MK11_HUMAN	MAPK11	physical	28514442

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 MAPK3_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"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: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.	19413330 [Abstract]

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