dbPTM

MP2K2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MP2K2_HUMAN
UniProt AC	P36507
Protein Name	Dual specificity mitogen-activated protein kinase kinase 2
Gene Name	MAP2K2
Organism	Homo sapiens (Human).
Sequence Length	400
Subcellular Localization	Cytoplasm . Membrane Peripheral membrane protein . Membrane localization is probably regulated by its interaction with KSR1.
Protein Description	Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity)..
Protein Sequence	MLARRKPVLPALTINPTIAEGPSPTSEGASEANLVDLQKKLEELELDEQQKKRLEAFLTQKAKVGELKDDDFERISELGAGNGGVVTKVQHRPSGLIMARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKEAKRIPEEILGKVSIAVLRGLAYLREKHQIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMAPERLQGTHYSVQSDIWSMGLSLVELAVGRYPIPPPDAKELEAIFGRPVVDGEEGEPHSISPRPRPPGRPVSGHGMDSRPAMAIFELLDYIVNEPPPKLPNGVFTPDFQEFVNKCLIKNPAERADLKMLTNHTFIKRSEVEEVDFAGWLCKTLRLNQPGTPTRTAV

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
1	Acetylation	-------MLARRKPV -------CCCCCCCC	6.27	19413330
6	Ubiquitination	--MLARRKPVLPALT --CCCCCCCCCCEEE	33.65	29967540
13	Acetylation	KPVLPALTINPTIAE CCCCCEEEECCCCCC	22.33	147945
13	Phosphorylation	KPVLPALTINPTIAE CCCCCEEEECCCCCC	22.33	28176443
13	O-linked_Glycosylation	KPVLPALTINPTIAE CCCCCEEEECCCCCC	22.33	30059200
17	Phosphorylation	PALTINPTIAEGPSP CEEEECCCCCCCCCC	28.47	29255136
23	Phosphorylation	PTIAEGPSPTSEGAS CCCCCCCCCCCCCCC	52.22	29255136
25	O-linked_Glycosylation	IAEGPSPTSEGASEA CCCCCCCCCCCCCHH	43.69	OGP
25	Phosphorylation	IAEGPSPTSEGASEA CCCCCCCCCCCCCHH	43.69	29255136
26	Phosphorylation	AEGPSPTSEGASEAN CCCCCCCCCCCCHHC	37.10	29255136
30	Phosphorylation	SPTSEGASEANLVDL CCCCCCCCHHCHHHH	48.36	29255136
30	O-linked_Glycosylation	SPTSEGASEANLVDL CCCCCCCCHHCHHHH	48.36	OGP
39	Ubiquitination	ANLVDLQKKLEELEL HCHHHHHHHHHHCCC	67.62	22817900
40	Ubiquitination	NLVDLQKKLEELELD CHHHHHHHHHHCCCH	48.44	21906983
51	Ubiquitination	LELDEQQKKRLEAFL CCCHHHHHHHHHHHH	39.28	21906983
52	Ubiquitination	ELDEQQKKRLEAFLT CCHHHHHHHHHHHHH	58.85	22817900
59	Phosphorylation	KRLEAFLTQKAKVGE HHHHHHHHHHHCCCC	22.90	-
61	Ubiquitination	LEAFLTQKAKVGELK HHHHHHHHHCCCCCC	44.96	21963094
63	Ubiquitination	AFLTQKAKVGELKDD HHHHHHHCCCCCCCC	58.78	27667366
68	Ubiquitination	KAKVGELKDDDFERI HHCCCCCCCCCHHHH	55.60	21906983
76	Phosphorylation	DDDFERISELGAGNG CCCHHHHHHCCCCCC	32.75	28450419
88	Ubiquitination	GNGGVVTKVQHRPSG CCCCEEEEEEECCCC	28.43	29967540
94	Phosphorylation	TKVQHRPSGLIMARK EEEEECCCCEEEEEE	46.30	-
98	Sulfoxidation	HRPSGLIMARKLIHL ECCCCEEEEEEEHHH	3.38	30846556
101	Acetylation	SGLIMARKLIHLEIK CCEEEEEEEHHHHCC	42.10	26051181
101	Ubiquitination	SGLIMARKLIHLEIK CCEEEEEEEHHHHCC	42.10	17623298
108	Acetylation	KLIHLEIKPAIRNQI EEHHHHCCHHHHHHH	21.01	25953088
108	Sumoylation	KLIHLEIKPAIRNQI EEHHHHCCHHHHHHH	21.01	-
108	Ubiquitination	KLIHLEIKPAIRNQI EEHHHHCCHHHHHHH	21.01	23000965
108	Sumoylation	KLIHLEIKPAIRNQI EEHHHHCCHHHHHHH	21.01	-
163	Ubiquitination	DQVLKEAKRIPEEIL HHHHHHHHCCCHHHH	52.53	29967540
172	Ubiquitination	IPEEILGKVSIAVLR CCHHHHHHHHHHHHH	29.39	17623298
174	Phosphorylation	EEILGKVSIAVLRGL HHHHHHHHHHHHHHH	14.33	20068231
187	2-Hydroxyisobutyrylation	GLAYLREKHQIMHRD HHHHHHHHHCCCCCC	34.08	-
196	Ubiquitination	QIMHRDVKPSNILVN CCCCCCCCHHHEEEC	47.20	21906983
198	Phosphorylation	MHRDVKPSNILVNSR CCCCCCHHHEEECCC	30.68	21406692
204	Phosphorylation	PSNILVNSRGEIKLC HHHEEECCCCCEEEC	33.90	21406692
209	Ubiquitination	VNSRGEIKLCDFGVS ECCCCCEEECCCCCC	38.47	22817900
216	Phosphorylation	KLCDFGVSGQLIDSM EECCCCCCHHHHHHH	22.62	22322096
222	Phosphorylation	VSGQLIDSMANSFVG CCHHHHHHHHHHCCC	16.89	22322096
222	Acetylation	VSGQLIDSMANSFVG CCHHHHHHHHHHCCC	16.89	20068231
226	Phosphorylation	LIDSMANSFVGTRSY HHHHHHHHCCCCCCC	16.27	21487005
226	Acetylation	LIDSMANSFVGTRSY HHHHHHHHCCCCCCC	16.27	17192257
230	Phosphorylation	MANSFVGTRSYMAPE HHHHCCCCCCCCCCH	15.90	29255136
244	Dephosphorylation	ERLQGTHYSVQSDIW HHHCCCCCCHHHHHH	15.46	10224087
255	Ubiquitination	SDIWSMGLSLVELAV HHHHHCCHHHHHHHH	2.40	17623298
259	Ubiquitination	SMGLSLVELAVGRYP HCCHHHHHHHHCCCC	35.98	17623298
268	Ubiquitination	AVGRYPIPPPDAKEL HHCCCCCCCCCHHHH	29.84	17623298
277	Ubiquitination	PDAKELEAIFGRPVV CCHHHHHHHHCCCEE	18.29	17623298
293	Phosphorylation	GEEGEPHSISPRPRP CCCCCCCCCCCCCCC	35.16	29255136
295	Phosphorylation	EGEPHSISPRPRPPG CCCCCCCCCCCCCCC	20.19	29255136
306	Phosphorylation	RPPGRPVSGHGMDSR CCCCCCCCCCCCCCC	27.96	23401153
312	Phosphorylation	VSGHGMDSRPAMAIF CCCCCCCCCHHHHHH	31.13	25850435
348	Ubiquitination	DFQEFVNKCLIKNPA CHHHHHHHHHCCCHH	25.72	17623298
352	Ubiquitination	FVNKCLIKNPAERAD HHHHHHCCCHHHHCC	43.88	17623298
361	Acetylation	PAERADLKMLTNHTF HHHHCCHHHHHCCCE	32.20	25953088
361	Ubiquitination	PAERADLKMLTNHTF HHHHCCHHHHHCCCE	32.20	29967540
370	Ubiquitination	LTNHTFIKRSEVEEV HHCCCEECHHHCEEE	45.76	29967540
372	Phosphorylation	NHTFIKRSEVEEVDF CCCEECHHHCEEECC	40.78	20068231
385	Ubiquitination	DFAGWLCKTLRLNQP CCHHHHHHHHCCCCC	48.72	32015554
386	Phosphorylation	FAGWLCKTLRLNQPG CHHHHHHHHCCCCCC	19.00	23403867
394	Phosphorylation	LRLNQPGTPTRTAV- HCCCCCCCCCCCCC-	28.33	29255136
396	O-linked_Glycosylation	LNQPGTPTRTAV--- CCCCCCCCCCCC---	40.25	30059200
396	Phosphorylation	LNQPGTPTRTAV--- CCCCCCCCCCCC---	40.25	29255136
398	O-linked_Glycosylation	QPGTPTRTAV----- CCCCCCCCCC-----	33.96	30059200
398	Phosphorylation	QPGTPTRTAV----- CCCCCCCCCC-----	33.96	23927012

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
59	T	Phosphorylation	Kinase	CHEK1	O14757	GPS
222	S	Phosphorylation	Kinase	BRAF	P15056	PSP
222	S	Phosphorylation	Kinase	MAP3K8	P41279	GPS
222	S	Phosphorylation	Kinase	PLK1	P53350	PSP
222	S	Phosphorylation	Kinase	RAF1	P04049	GPS
222	S	Phosphorylation	Kinase	RAF	-	Uniprot
226	S	Phosphorylation	Kinase	BRAF	P15056	PSP
226	S	Phosphorylation	Kinase	MAP3K8	P41279	GPS
226	S	Phosphorylation	Kinase	PDK1	Q15118	GPS
226	S	Phosphorylation	Kinase	PDPK1	O15530	PhosphoELM
226	S	Phosphorylation	Kinase	PLK1	P53350	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
222	S	Acetylation	17116858
(Microbial infection) Acetylation of Ser-222 and Ser-226 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.
222	S	Phosphorylation	17116858
(Microbial infection) Acetylation of Ser-222 and Ser-226 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.
226	S	Acetylation	17116858
(Microbial infection) Acetylation of Ser-222 and Ser-226 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.
226	S	Phosphorylation	17116858
(Microbial infection) Acetylation of Ser-222 and Ser-226 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.

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 MP2K2_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
ARAF_HUMAN	ARAF	physical	11909642
FLNA_MOUSE	Flna	physical	9006895
MK03_HUMAN	MAPK3	physical	9006895
MK01_HUMAN	MAPK1	physical	11823456
MK03_HUMAN	MAPK3	physical	8626767
MP2K2_HUMAN	MAP2K2	physical	8226933
MK03_HUMAN	MAPK3	physical	8226933
CSN5_HUMAN	COPS5	physical	20936779
KSR1_MOUSE	Ksr1	physical	10409742
WDR83_HUMAN	WDR83	physical	15118098
RAF1_HUMAN	RAF1	physical	9808624
MK01_HUMAN	MAPK1	physical	12788955
RAF1_HUMAN	RAF1	physical	21988832
ZN207_HUMAN	ZNF207	physical	21988832
CCDB1_HUMAN	CCNDBP1	physical	25416956
THIO_HUMAN	TXN	physical	26344197
MP2K1_HUMAN	MAP2K1	physical	28514442
TBA4A_HUMAN	TUBA4A	physical	28514442
NOCT_HUMAN	CCRN4L	physical	28514442

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
615280	Cardiofaciocutaneous syndrome 4 (CFC4)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
DB06616	Bosutinib
DB08911	Trametinib

Regulatory Network of MP2K2_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, PHOSPHORYLATION [LARGESCALE ANALYSIS] AT THR-394, AND MASS SPECTROMETRY.	19413330 [Abstract]
Phosphorylation
Reference	PubMed
"Large-scale proteomics analysis of the human kinome."; Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.; Mol. Cell. Proteomics 8:1751-1764(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23; SER-222; SER-226;SER-293; SER-295 AND THR-396, AND MASS SPECTROMETRY.	19369195 [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 SER-222; SER-226; THR-394AND THR-396, AND MASS SPECTROMETRY.	18669648 [Abstract]
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle."; Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.; Mol. Cell 31:438-448(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23; SER-293; SER-295 ANDTHR-396, AND MASS SPECTROMETRY.	18691976 [Abstract]
"Proteomics analysis of protein kinases by target class-selectiveprefractionation and tandem mass spectrometry."; Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R.,Keri G., Wehland J., Daub H.; Mol. Cell. Proteomics 6:537-547(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226 AND THR-394, ANDMASS SPECTROMETRY.	17192257 [Abstract]
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks."; Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.; Cell 127:635-648(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23 AND THR-394, AND MASSSPECTROMETRY.	17081983 [Abstract]
"Acetylation of MEK2 and I kappa B kinase (IKK) activation loopresidues by YopJ inhibits signaling."; Mittal R., Peak-Chew S.Y., McMahon H.T.; Proc. Natl. Acad. Sci. U.S.A. 103:18574-18579(2006). Cited for: PROTEIN SEQUENCE OF 210-231, INACTIVATION BY YERSINIA YOPJ,PHOSPHORYLATION AT SER-222 AND SER-226, ACETYLATION AT SER-222 ANDSER-226, AND MASS SPECTROMETRY.	17116858 [Abstract]
"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-394, AND MASSSPECTROMETRY.	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: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGESCALE ANALYSIS] AT THR-394, AND MASS SPECTROMETRY.	19413330 [Abstract]
"Phosphoproteome of resting human platelets."; Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,Schuetz C., Walter U., Gambaryan S., Sickmann A.; J. Proteome Res. 7:526-534(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-394 AND THR-396, ANDMASS SPECTROMETRY.	18088087 [Abstract]
"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column."; Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.; Anal. Sci. 24:161-166(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-396, AND MASSSPECTROMETRY.	18187866 [Abstract]
"A probability-based approach for high-throughput proteinphosphorylation analysis and site localization."; Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; Nat. Biotechnol. 24:1285-1292(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-396, AND MASSSPECTROMETRY.	16964243 [Abstract]
"Large-scale characterization of HeLa cell nuclear phosphoproteins."; Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J.,Li J., Cohn M.A., Cantley L.C., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-394, AND MASSSPECTROMETRY.	15302935 [Abstract]

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