dbPTM

MP2K7_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MP2K7_HUMAN
UniProt AC	O14733
Protein Name	Dual specificity mitogen-activated protein kinase kinase 7
Gene Name	MAP2K7
Organism	Homo sapiens (Human).
Sequence Length	419
Subcellular Localization	Nucleus. Cytoplasm.
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 MAP2K4/MKK4, 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/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis..
Protein Sequence	MAASSLEQKLSRLEAKLKQENREARRRIDLNLDISPQRPRPTLQLPLANDGGSRSPSSESSPQHPTPPARPRHMLGLPSTLFTPRSMESIEIDQKLQEIMKQTGYLTIGGQRYQAEINDLENLGEMGSGTCGQVWKMRFRKTGHVIAVKQMRRSGNKEENKRILMDLDVVLKSHDCPYIVQCFGTFITNTDVFIAMELMGTCAEKLKKRMQGPIPERILGKMTVAIVKALYYLKEKHGVIHRDVKPSNILLDERGQIKLCDFGISGRLVDSKAKTRSAGCAAYMAPERIDPPDPTKPDYDIRADVWSLGISLVELATGQFPYKNCKTDFEVLTKVLQEEPPLLPGHMGFSGDFQSFVKDCLTKDHRKRPKYNKLLEHSFIKRYETLEVDVASWFKDVMAKTESPRTSGVLSQPHLPFFR

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MAASSLEQK ------CCCHHHHHH	18.95	22814378
5	Phosphorylation	---MAASSLEQKLSR ---CCCHHHHHHHHH	31.06	24719451
9	Ubiquitination	AASSLEQKLSRLEAK CCHHHHHHHHHHHHH	38.77	-
9 (in isoform 2)	Ubiquitination	-	38.77	-
35	Phosphorylation	IDLNLDISPQRPRPT HCCCCCCCCCCCCCE	18.04	22167270
42	Phosphorylation	SPQRPRPTLQLPLAN CCCCCCCEEEEECCC	28.54	22496350
53	Phosphorylation	PLANDGGSRSPSSES ECCCCCCCCCCCCCC	34.80	20873877
55	Phosphorylation	ANDGGSRSPSSESSP CCCCCCCCCCCCCCC	30.72	27794612
57	Phosphorylation	DGGSRSPSSESSPQH CCCCCCCCCCCCCCC	48.24	27794612
58	Phosphorylation	GGSRSPSSESSPQHP CCCCCCCCCCCCCCC	44.90	27794612
60	Phosphorylation	SRSPSSESSPQHPTP CCCCCCCCCCCCCCC	49.63	21712546
61	Phosphorylation	RSPSSESSPQHPTPP CCCCCCCCCCCCCCC	25.24	23401153
66	Phosphorylation	ESSPQHPTPPARPRH CCCCCCCCCCCCCCH	39.52	26055452
79	Phosphorylation	RHMLGLPSTLFTPRS CHHCCCCCCCCCCCC	42.67	29396449
80	Phosphorylation	HMLGLPSTLFTPRSM HHCCCCCCCCCCCCH	24.77	28555341
83	Phosphorylation	GLPSTLFTPRSMESI CCCCCCCCCCCHHHC	22.39	29396449
86	Phosphorylation	STLFTPRSMESIEID CCCCCCCCHHHCCHH	28.27	20068231
87	Sulfoxidation	TLFTPRSMESIEIDQ CCCCCCCHHHCCHHH	5.03	21406390
89	Phosphorylation	FTPRSMESIEIDQKL CCCCCHHHCCHHHHH	19.51	20068231
95	Ubiquitination	ESIEIDQKLQEIMKQ HHCCHHHHHHHHHHH	48.68	21906983
95 (in isoform 1)	Ubiquitination	-	48.68	21890473
95 (in isoform 2)	Ubiquitination	-	48.68	21890473
95 (in isoform 4)	Ubiquitination	-	48.68	21890473
101	Ubiquitination	QKLQEIMKQTGYLTI HHHHHHHHHHCCEEE	50.82	-
105	Phosphorylation	EIMKQTGYLTIGGQR HHHHHHCCEEECCEE	12.22	29496907
111 (in isoform 3)	Ubiquitination	-	35.38	21890473
141	Ubiquitination	VWKMRFRKTGHVIAV HHEEEEECCCCEEEE	57.03	-
142	Phosphorylation	WKMRFRKTGHVIAVK HEEEEECCCCEEEEE	28.41	-
146 (in isoform 2)	Phosphorylation	-	2.79	27732954
149	Ubiquitination	TGHVIAVKQMRRSGN CCCEEEEEEHHHCCC	29.38	-
149	Acetylation	TGHVIAVKQMRRSGN CCCEEEEEEHHHCCC	29.38	25953088
150 (in isoform 2)	Phosphorylation	-	24.82	26425664
152 (in isoform 2)	Phosphorylation	-	27.41	27732954
153 (in isoform 2)	Phosphorylation	-	43.50	26425664
221	Ubiquitination	IPERILGKMTVAIVK CCHHHHHHHHHHHHH	28.14	-
234	Ubiquitination	VKALYYLKEKHGVIH HHHHHHHHHHHCEEC	48.90	-
245 (in isoform 4)	Ubiquitination	-	47.20	21890473
245	Ubiquitination	GVIHRDVKPSNILLD CEECCCCCHHHEEEC	47.20	21906983
245 (in isoform 1)	Ubiquitination	-	47.20	21890473
258	Ubiquitination	LDERGQIKLCDFGIS ECCCCCEEECCCCCC	34.86	-
261 (in isoform 3)	Ubiquitination	-	56.07	21890473
265	Phosphorylation	KLCDFGISGRLVDSK EECCCCCCCEECCCC	20.45	21815630
271	Phosphorylation	ISGRLVDSKAKTRSA CCCEECCCCCCCCCC	27.34	23312004
275	Phosphorylation	LVDSKAKTRSAGCAA ECCCCCCCCCCCCCH	34.41	9312068
277	Phosphorylation	DSKAKTRSAGCAAYM CCCCCCCCCCCCHHC	33.96	27251275
283	Phosphorylation	RSAGCAAYMAPERID CCCCCCHHCCCCCCC	3.85	-
284	Sulfoxidation	SAGCAAYMAPERIDP CCCCCHHCCCCCCCC	4.26	21406390
288 (in isoform 2)	Ubiquitination	-	37.24	21890473
301 (in isoform 2)	Ubiquitination	-	2.97	-
326	Ubiquitination	QFPYKNCKTDFEVLT CCCCCCCCCHHHHHH	61.60	-
358	Ubiquitination	GDFQSFVKDCLTKDH CCHHHHHHHHHCCCH	40.49	-
369 (in isoform 2)	Ubiquitination	-	46.66	-
371	Phosphorylation	DHRKRPKYNKLLEHS CHHHCHHHHHHHHCH	21.88	29083192
373	Acetylation	RKRPKYNKLLEHSFI HHCHHHHHHHHCHHH	51.89	25953088
373 (in isoform 1)	Ubiquitination	-	51.89	21890473
373	Ubiquitination	RKRPKYNKLLEHSFI HHCHHHHHHHHCHHH	51.89	2189047
378	Phosphorylation	YNKLLEHSFIKRYET HHHHHHCHHHHHCCE	21.20	20873877
380 (in isoform 4)	Ubiquitination	-	2.52	21890473
389 (in isoform 3)	Ubiquitination	-	22.38	21890473
400	Ubiquitination	WFKDVMAKTESPRTS HHHHHHHHCCCCCCC	34.43	-
401	Phosphorylation	FKDVMAKTESPRTSG HHHHHHHCCCCCCCC	31.96	22617229
403	Phosphorylation	DVMAKTESPRTSGVL HHHHHCCCCCCCCCC	25.55	25159151
406	Phosphorylation	AKTESPRTSGVLSQP HHCCCCCCCCCCCCC	32.96	25159151
407	Phosphorylation	KTESPRTSGVLSQPH HCCCCCCCCCCCCCC	28.34	25159151
411	Phosphorylation	PRTSGVLSQPHLPFF CCCCCCCCCCCCCCC	38.98	9535930
416 (in isoform 2)	Ubiquitination	-	24.24	21890473
443 (in isoform 2)	Ubiquitination	-		-

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
271	S	Phosphorylation	Kinase	MAP3K1	Q13233	GPS
271	S	Phosphorylation	Kinase	MAP3K	-	Uniprot
275	T	Phosphorylation	Kinase	MAP3K1	Q13233	GPS
275	T	Phosphorylation	Kinase	MAP3K	-	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
271	S	Phosphorylation	-
Activated by phosphorylation on Ser-271 and Thr-275 by MAP kinase kinase kinases (MAP3Ks).
275	T	Phosphorylation	-
Activated by phosphorylation on Ser-271 and Thr-275 by MAP kinase kinase kinases (MAP3Ks).

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 MP2K7_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
JIP1_HUMAN	MAPK8IP1	physical	10490659
JIP2_HUMAN	MAPK8IP2	physical	10490659
M3K5_HUMAN	MAP3K5	physical	11959862
MK08_HUMAN	MAPK8	physical	9207092
MK08_HUMAN	MAPK8	physical	10713157
M3K1_HUMAN	MAP3K1	physical	15866172
M3K4_HUMAN	MAP3K4	physical	15866172
MK08_HUMAN	MAPK8	physical	16533805
JUN_HUMAN	JUN	physical	13130464
WDR6_HUMAN	WDR6	physical	19910486
BCL10_HUMAN	BCL10	physical	17189706
MK08_HUMAN	MAPK8	physical	12821118
MK09_HUMAN	MAPK9	physical	12821118
RL30_HUMAN	RPL30	physical	21988832
MK08_HUMAN	MAPK8	physical	24975362
ALDOA_HUMAN	ALDOA	physical	26344197
GSK3B_HUMAN	GSK3B	physical	26344197
CH10_HUMAN	HSPE1	physical	26344197
ILKAP_HUMAN	ILKAP	physical	26344197
MP2K4_HUMAN	MAP2K4	physical	13130464
MK08_HUMAN	MAPK8	physical	13130464
MK01_HUMAN	MAPK1	physical	7499408
MK01_HUMAN	MAPK1	physical	15192046

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 MP2K7_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 ALA-2, AND MASS SPECTROMETRY.	19413330 [Abstract]

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