dbPTM

MK09_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MK09_HUMAN
UniProt AC	P45984
Protein Name	Mitogen-activated protein kinase 9
Gene Name	MAPK9
Organism	Homo sapiens (Human).
Sequence Length	424
Subcellular Localization	Cytoplasm . Nucleus . Colocalizes with POU5F1 in the nucleus.
Protein Description	Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock. [PubMed: 22441692 Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation (By similarity; MAPK9 isoforms display different binding patterns: alpha-1 and alpha-2 preferentially bind to JUN, whereas beta-1 and beta-2 bind to ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only weakly to it.]
Protein Sequence	MSDSKCDSQFYSVQVADSTFTVLKRYQQLKPIGSGAQGIVCAAFDTVLGINVAVKKLSRPFQNQTHAKRAYRELVLLKCVNHKNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQVIHMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTACTNFMMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGELVKGCVIFQGTDHIDQWNKVIEQLGTPSAEFMKKLQPTVRNYVENRPKYPGIKFEELFPDWIFPSESERDKIKTSQARDLLSKMLVIDPDKRISVDEALRHPYITVWYDPAEAEAPPPQIYDAQLEEREHAIEEWKELIYKEVMDWEERSKNGVVKDQPSDAAVSSNATPSQSSSINDISSMSTEQTLASDTDSSLDASTGPLEGCR

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
56	Ubiquitination	GINVAVKKLSRPFQN HHHHHHHHHCCCCCC	45.13	-
68	Ubiquitination	FQNQTHAKRAYRELV CCCHHHHHHHHHHHH	29.92	-
93	Phosphorylation	ISLLNVFTPQKTLEE HHHHCCCCCCHHHHH	22.11	11823425
129	Phosphorylation	ELDHERMSYLLYQML CCCHHHHHHHHHHHH	20.89	24043423
130	Phosphorylation	LDHERMSYLLYQMLC CCHHHHHHHHHHHHH	7.44	24043423
133	Phosphorylation	ERMSYLLYQMLCGIK HHHHHHHHHHHHCHH	6.84	24043423
144	Phosphorylation	CGIKHLHSAGIIHRD HCHHHHHHCCEECCC	34.25	-
153	Ubiquitination	GIIHRDLKPSNIVVK CEECCCCCHHHEEEE	51.17	-
155	Phosphorylation	IHRDLKPSNIVVKSD ECCCCCHHHEEEECC	37.29	22817900
160	Ubiquitination	KPSNIVVKSDCTLKI CHHHEEEECCCEEEE	29.68	-
163	S-nitrosocysteine	NIVVKSDCTLKILDF HEEEECCCEEEEHHH	6.57	-
163	S-nitrosylation	NIVVKSDCTLKILDF HEEEECCCEEEEHHH	6.57	19483679
166	Ubiquitination	VKSDCTLKILDFGLA EECCCEEEEHHHHHH	24.06	-
175	Phosphorylation	LDFGLARTACTNFMM HHHHHHHHHCCHHHC	22.07	21945579
178	Phosphorylation	GLARTACTNFMMTPY HHHHHHCCHHHCCCH	29.09	21945579
183	Phosphorylation	ACTNFMMTPYVVTRY HCCHHHCCCHHHHHH	10.32	22322096
185	Phosphorylation	TNFMMTPYVVTRYYR CHHHCCCHHHHHHHC	9.82	22322096
188	Phosphorylation	MMTPYVVTRYYRAPE HCCCHHHHHHHCCCH	11.69	21945579
250 (in isoform 3)	Ubiquitination	-	56.50	21890473
250 (in isoform 2)	Ubiquitination	-	56.50	21890473
250 (in isoform 4)	Ubiquitination	-	56.50	21890473
250 (in isoform 1)	Ubiquitination	-	56.50	21890473
250	Ubiquitination	TPSAEFMKKLQPTVR CCCHHHHHHHHHHHH	56.50	21906983
250	Acetylation	TPSAEFMKKLQPTVR CCCHHHHHHHHHHHH	56.50	20167786
251	Ubiquitination	PSAEFMKKLQPTVRN CCHHHHHHHHHHHHH	40.33	-
292	Phosphorylation	ERDKIKTSQARDLLS HHHHCCHHHHHHHHH	19.48	-
300	Ubiquitination	QARDLLSKMLVIDPD HHHHHHHHHCEECCC	35.90	-
308	2-Hydroxyisobutyrylation	MLVIDPDKRISVDEA HCEECCCCCCCHHHH	57.95	-
311	Phosphorylation	IDPDKRISVDEALRH ECCCCCCCHHHHHCC	27.78	22673903
353 (in isoform 2)	Ubiquitination	-	46.02	21890473
353 (in isoform 4)	Ubiquitination	-	46.02	21890473
353 (in isoform 3)	Ubiquitination	-	46.02	21890473
353 (in isoform 1)	Ubiquitination	-	46.02	21890473
353	Ubiquitination	EHAIEEWKELIYKEV HHHHHHHHHHHHHHH	46.02	21890473
353	Ubiquitination	EHAIEEWKELIYKEV HHHHHHHHHHHHHHH	46.02	21890473
357	Phosphorylation	EEWKELIYKEVMDWE HHHHHHHHHHHCCHH	17.45	25072903
361	Sulfoxidation	ELIYKEVMDWEERSK HHHHHHHCCHHHHHH	5.34	30846556
388	Phosphorylation	VSSNATPSQSSSIND CCCCCCCCCCCCHHH	38.04	28348404
390	Phosphorylation	SNATPSQSSSINDIS CCCCCCCCCCHHHHH	30.32	28348404
391	Phosphorylation	NATPSQSSSINDISS CCCCCCCCCHHHHHC	27.83	28348404
392	Phosphorylation	ATPSQSSSINDISSM CCCCCCCCHHHHHCC	30.56	28348404
397	Phosphorylation	SSSINDISSMSTEQT CCCHHHHHCCCHHHH	23.89	28348404
398	Phosphorylation	SSINDISSMSTEQTL CCHHHHHCCCHHHHH	19.65	28348404
400	Phosphorylation	INDISSMSTEQTLAS HHHHHCCCHHHHHHC	30.64	28348404
401	Phosphorylation	NDISSMSTEQTLASD HHHHCCCHHHHHHCC	24.38	28348404
404	Phosphorylation	SSMSTEQTLASDTDS HCCCHHHHHHCCCCC	20.33	11062067
407	Phosphorylation	STEQTLASDTDSSLD CHHHHHHCCCCCCCC	44.12	11062067
409	Phosphorylation	EQTLASDTDSSLDAS HHHHHCCCCCCCCCC	34.97	29802988
411	Phosphorylation	TLASDTDSSLDASTG HHHCCCCCCCCCCCC	34.59	28348404
412	Phosphorylation	LASDTDSSLDASTGP HHCCCCCCCCCCCCC	32.83	27251275

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
183	T	Phosphorylation	Kinase	MP2K7	O14733	PhosphoELM
185	Y	Phosphorylation	Kinase	MP2K4	P45985	PhosphoELM
185	Y	Phosphorylation	Kinase	RET	P07949	PSP
404	T	Phosphorylation	Kinase	CSNK2A1	P68400	GPS
404	T	Phosphorylation	Kinase	MAP2K7	O14733	GPS
404	T	Phosphorylation	Kinase	MAP2K-FAMILY	-	GPS
404	T	Phosphorylation	Kinase	MAP2K_GROUP	-	PhosphoELM
407	S	Phosphorylation	Kinase	CSNK2A1	P68400	GPS
407	S	Phosphorylation	Kinase	MAP2K7	O14733	GPS
407	S	Phosphorylation	Kinase	MAP2K-FAMILY	-	GPS
407	S	Phosphorylation	Kinase	MAP2K_GROUP	-	PhosphoELM
-	K	Ubiquitination	E3 ubiquitin ligase	FZR1	Q9UM11	PMID:20581839

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
183	T	Phosphorylation		11062067
Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme.

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 MK09_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CEP44_HUMAN	CEP44	physical	16189514
ZBT25_HUMAN	ZBTB25	physical	16189514
SF3B4_HUMAN	SF3B4	physical	16189514
WDR62_HUMAN	WDR62	physical	16189514
XPP1_HUMAN	XPNPEP1	physical	16169070
XPO7_HUMAN	XPO7	physical	16169070
PPA5_HUMAN	ACP5	physical	16169070
CE126_HUMAN	KIAA1377	physical	16169070
KPCD1_HUMAN	PRKD1	physical	11948398
JIP1_HUMAN	MAPK8IP1	physical	10490659
JIP2_HUMAN	MAPK8IP2	physical	10490659
KS6B1_MOUSE	Rps6kb1	physical	11279232
P53_MOUSE	Trp53	physical	9393873
JUNB_HUMAN	JUNB	physical	8945519
JUN_HUMAN	JUN	physical	8945519
TOB1_HUMAN	TOB1	physical	12151396
P53_HUMAN	TP53	physical	12384512
MACF1_HUMAN	MACF1	physical	20936779
HDAC9_HUMAN	HDAC9	physical	16611996
NFAC2_HUMAN	NFATC2	physical	15184502
MFN2_HUMAN	MFN2	physical	22748923
MP2K4_HUMAN	MAP2K4	physical	22366412
PRKDC_HUMAN	PRKDC	physical	22366412
JUN_HUMAN	JUN	physical	8985011
M3K1_HUMAN	MAP3K1	physical	12228228
JUN_HUMAN	JUN	physical	10490605
JUN_HUMAN	JUN	physical	16533805
MP2K7_HUMAN	MAP2K7	physical	16533805
ATF2_HUMAN	ATF2	physical	16533805
JIP1_HUMAN	MAPK8IP1	physical	15998799
CTNB1_HUMAN	CTNNB1	physical	19667122
JUN_HUMAN	JUN	physical	19527717
STK25_HUMAN	STK25	physical	22939629
PKN1_HUMAN	PKN1	physical	22939629
JUN_HUMAN	JUN	physical	8654373
ATF2_HUMAN	ATF2	physical	8654373
ELK1_HUMAN	ELK1	physical	8654373
JUND_HUMAN	JUND	physical	8654373
JUNB_HUMAN	JUNB	physical	8654373
JUN_HUMAN	JUN	physical	8001819
WDR62_HUMAN	WDR62	physical	19910486
JUN_HUMAN	JUN	physical	19910486
JUN_HUMAN	JUN	physical	17189706
BCL10_HUMAN	BCL10	physical	17189706
RARG_MOUSE	Rarg	physical	10383391
RARA_MOUSE	Rara	physical	10383391
IRF3_HUMAN	IRF3	physical	19153595
JUN_HUMAN	JUN	physical	16824735
NFAC4_HUMAN	NFATC4	physical	17875713
NFAC3_HUMAN	NFATC3	physical	17875713
ELK1_HUMAN	ELK1	physical	17875713
JUN_HUMAN	JUN	physical	17875713
ATF2_HUMAN	ATF2	physical	17875713
MK09_HUMAN	MAPK9	physical	19204086
ELK1_HUMAN	ELK1	physical	8846788
ARRB2_HUMAN	ARRB2	physical	19060904
JUN_HUMAN	JUN	physical	11278395
M3K10_HUMAN	MAP3K10	physical	11278395
MPIP3_HUMAN	CDC25C	physical	15629715
JUN_HUMAN	JUN	physical	12788955
ATF2_HUMAN	ATF2	physical	12788955
NCF1_HUMAN	NCF1	physical	15629715
MPIP2_HUMAN	CDC25B	physical	15629715
SSU72_HUMAN	SSU72	physical	21988832
TUSC2_HUMAN	TUSC2	physical	21988832
MK10_HUMAN	MAPK10	physical	23602568
MK09_HUMAN	MAPK9	physical	23602568
MK08_HUMAN	MAPK8	physical	23602568
DUS8_HUMAN	DUSP8	physical	23602568
SPTN1_HUMAN	SPTAN1	physical	23602568
LAMA1_HUMAN	LAMA1	physical	23602568
FRIH_HUMAN	FTH1	physical	23602568
SEC13_HUMAN	SEC13	physical	23602568
DHX33_HUMAN	DHX33	physical	23602568
ATF2_HUMAN	ATF2	physical	11865055
GLYC_HUMAN	SHMT1	physical	25416956
SF3B4_HUMAN	SF3B4	physical	25416956
TEX11_HUMAN	TEX11	physical	25416956
CCD33_HUMAN	CCDC33	physical	25416956
EFHC2_HUMAN	EFHC2	physical	25416956
CEP44_HUMAN	CEP44	physical	25416956
LMBL3_HUMAN	L3MBTL3	physical	25416956
LNX1_HUMAN	LNX1	physical	25416956
CA094_HUMAN	C1orf94	physical	25416956
WDR62_HUMAN	WDR62	physical	25416956
SMCO3_HUMAN	SMCO3	physical	25416956
AKT1_HUMAN	AKT1	physical	20186153
H15_HUMAN	HIST1H1B	physical	26186194
SPB5_HUMAN	SERPINB5	physical	26186194
KC1E_HUMAN	CSNK1E	physical	26186194
DUS14_HUMAN	DUSP14	physical	26186194
PKP3_HUMAN	PKP3	physical	26186194
LRC15_HUMAN	LRRC15	physical	26186194
DSG4_HUMAN	DSG4	physical	26186194
PPM1A_HUMAN	PPM1A	physical	26344197
STK25_HUMAN	STK25	physical	26344197
STK26_HUMAN	STK26	physical	26344197
NFAC2_HUMAN	NFATC2	physical	15958558
DUS14_HUMAN	DUSP14	physical	28514442
PKP3_HUMAN	PKP3	physical	28514442
H15_HUMAN	HIST1H1B	physical	28514442
LRC15_HUMAN	LRRC15	physical	28514442
SPB5_HUMAN	SERPINB5	physical	28514442
B2CL1_HUMAN	BCL2L1	physical	22617334
JUN_HUMAN	JUN	physical	9596579
PSN1_HUMAN	PSEN1	physical	18667537
NICA_HUMAN	NCSTN	physical	18667537

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 MK09_HUMAN

Related Literatures of Post-Translational Modification

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 THR-183; TYR-185 ANDTHR-404, AND MASS SPECTROMETRY.	19369195 [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 THR-183 AND TYR-185, ANDMASS SPECTROMETRY.	17192257 [Abstract]
"An extensive survey of tyrosine phosphorylation revealing new sitesin human mammary epithelial cells."; Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A.,Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D.,Wiley H.S., Qian W.-J.; J. Proteome Res. 8:3852-3861(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-185, AND MASSSPECTROMETRY.	19534553 [Abstract]
"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer."; Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; Cell 131:1190-1203(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-185, AND MASSSPECTROMETRY.	18083107 [Abstract]

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