dbPTM

MK10_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MK10_HUMAN	Jmol._Canvas2D (Jmol) "myJmol"[x]
UniProt AC	P53779
Protein Name	Mitogen-activated protein kinase 10
Gene Name	MAPK10
Organism	Homo sapiens (Human).
Sequence Length	464
Subcellular Localization	Cytoplasm . Membrane Lipid-anchor . Nucleus . Mitochondrion . Palmitoylation regulates MAPK10 trafficking to cytoskeleton. Recruited to the mitochondria in the presence of SARM1 (By similarity)..
Protein Description	Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration 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 MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the amyloid-beta precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the photic regulation of the circadian clock. [PubMed: 22441692]
Protein Sequence	MSLHFLYYCSEPTLDVKIAFCQGFDKQVDVSYIAKHYNMSKSKVDNQFYSVEVGDSTFTVLKRYQNLKPIGSGAQGIVCAAYDAVLDRNVAIKKLSRPFQNQTHAKRAYRELVLMKCVNHKNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQVIQMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGEMVRHKILFPGRDYIDQWNKVIEQLGTPCPEFMKKLQPTVRNYVENRPKYAGLTFPKLFPDSLFPADSEHNKLKASQARDLLSKMLVIDPAKRISVDDALQHPYINVWYDPAEVEAPPPQIYDKQLDEREHTIEEWKELIYKEVMNSEEKTKNGVVKGQPSPSGAAVNSSESLPPSSSVNDISSMSTDQTLASDTDSSLEASAGPLGCCR

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Phosphorylation	------MSLHFLYYC ------CCEEEEEEC	30.47	24114839
7	Phosphorylation	-MSLHFLYYCSEPTL -CCEEEEEECCCCCE	11.07	24114839
8	Phosphorylation	MSLHFLYYCSEPTLD CCEEEEEECCCCCEE	7.52	27732954
10	Phosphorylation	LHFLYYCSEPTLDVK EEEEEECCCCCEEEE	30.41	24114839
13	Phosphorylation	LYYCSEPTLDVKIAF EEECCCCCEEEEEEE	31.38	24114839
94	Ubiquitination	DRNVAIKKLSRPFQN CCCHHHHHHCCCCCC	45.65	-
106	Ubiquitination	FQNQTHAKRAYRELV CCCHHHHHHHHHHHH	29.92	-
131	Phosphorylation	ISLLNVFTPQKTLEE HHHHCCCCCCHHHHH	22.11	11823425
135	Phosphorylation	NVFTPQKTLEEFQDV CCCCCCHHHHHHHHH	33.87	23607784
143	Phosphorylation	LEEFQDVYLVMELMD HHHHHHHHHHHHHCC	11.23	23607784
167	Phosphorylation	ELDHERMSYLLYQML CCCHHHHHHHHHHHH	20.89	24043423
168	Phosphorylation	LDHERMSYLLYQMLC CCHHHHHHHHHHHHH	7.44	24043423
171	Phosphorylation	ERMSYLLYQMLCGIK HHHHHHHHHHHHCHH	6.84	24043423
182	Phosphorylation	CGIKHLHSAGIIHRD HCHHHHHHCCEECCC	34.25	-
191	Ubiquitination	GIIHRDLKPSNIVVK CEECCCCCHHHEEEE	51.17	-
193	Phosphorylation	IHRDLKPSNIVVKSD ECCCCCHHHEEEECC	37.29	22817900
198	Ubiquitination	KPSNIVVKSDCTLKI CHHHEEEECCCEEEE	29.68	-
204	Ubiquitination	VKSDCTLKILDFGLA EECCCEEEEECHHCC	24.06	-
213	Phosphorylation	LDFGLARTAGTSFMM ECHHCCCCCCCCCCC	24.67	21945579
216	Phosphorylation	GLARTAGTSFMMTPY HCCCCCCCCCCCCCH	19.14	21945579
217	Phosphorylation	LARTAGTSFMMTPYV CCCCCCCCCCCCCHH	15.38	21945579
221	Phosphorylation	AGTSFMMTPYVVTRY CCCCCCCCCHHEEEH	10.32	22322096
223	Phosphorylation	TSFMMTPYVVTRYYR CCCCCCCHHEEEHHC	9.82	22322096
226	Phosphorylation	MMTPYVVTRYYRAPE CCCCHHEEEHHCCCH	11.69	21945579
281	Phosphorylation	KVIEQLGTPCPEFMK HHHHHHCCCCHHHHH	30.25	-
288	Ubiquitination	TPCPEFMKKLQPTVR CCCHHHHHHHHHHHH	56.50	-
289	Ubiquitination	PCPEFMKKLQPTVRN CCHHHHHHHHHHHHH	40.33	-
330	Phosphorylation	EHNKLKASQARDLLS HHCHHCHHHHHHHHH	23.84	-
346	Acetylation	MLVIDPAKRISVDDA HCCCCHHHCCCHHHH	56.50	129951
391	Ubiquitination	EHTIEEWKELIYKEV CHHHHHHHHHHHHHH	46.02	-
415	Phosphorylation	GVVKGQPSPSGAAVN CEECCCCCCCCCCCC	24.66	19369195
415 (in isoform 2)	Phosphorylation	-	24.66	18691976
417	Phosphorylation	VKGQPSPSGAAVNSS ECCCCCCCCCCCCCC	45.46	19369195
417 (in isoform 2)	Phosphorylation	-	45.46	19369195
462	S-palmitoylation	ASAGPLGCCR----- HHCCCCCCCC-----	2.02	21941371
463	S-palmitoylation	SAGPLGCCR------ HCCCCCCCC------	5.70	21941371

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
221	T	Phosphorylation	Kinase	MP2K7	O14733	PhosphoELM
221	T	Phosphorylation	Kinase	MAP2K7	O14733	GPS
221	T	Phosphorylation	Kinase	MAP2K-FAMILY	-	GPS
221	T	Phosphorylation	Kinase	MAP2K_GROUP	-	PhosphoELM
223	Y	Phosphorylation	Kinase	MP2K4	P45985	PhosphoELM
223	Y	Phosphorylation	Kinase	MAP2K4	P45985	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	FZR1	Q9UM11	PMID:20581839

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
221	T	Phosphorylation	10715136
Dually phosphorylated on Thr-221 and Tyr-223 by MAP2K4 and MAP2K7, which activates the enzyme.
221	T	Phosphorylation	10715136
MAP2K7 shows a strong preference for Thr-221 while MAP2K4 phosphorylates Tyr-223 preferentially.

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 MK10_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
JIP3_HUMAN	MAPK8IP3	physical	10523642
TF3C1_HUMAN	GTF3C1	physical	16169070
U119A_HUMAN	UNC119	physical	16169070
ARRB2_HUMAN	ARRB2	physical	11356842
ARRB1_HUMAN	ARRB1	physical	11356842
P53_MOUSE	Trp53	physical	9393873
JIP3_HUMAN	MAPK8IP3	physical	12189133
MCL1_HUMAN	MCL1	physical	17670986
CBP_HUMAN	CREBBP	physical	20936779
CE290_HUMAN	CEP290	physical	20936779
KI26A_HUMAN	KIF26A	physical	20936779
HDAC9_HUMAN	HDAC9	physical	16611996
PLIN2_HUMAN	PLIN2	physical	18624398
JUN_HUMAN	JUN	physical	19527717
A4_HUMAN	APP	physical	21832049
JUN_HUMAN	JUN	physical	8654373
ATF2_HUMAN	ATF2	physical	8654373
ELK1_HUMAN	ELK1	physical	8654373
RARA_MOUSE	Rara	physical	10383391
JUN_HUMAN	JUN	physical	16824735
PMYT1_HUMAN	PKMYT1	physical	19204086
MK10_HUMAN	MAPK10	physical	19204086
CDN2A_HUMAN	CDKN2A	physical	16007099
ARF_HUMAN	CDKN2A	physical	16007099
CDN2C_HUMAN	CDKN2C	physical	16007099
JUN_HUMAN	JUN	physical	16007099
ARRB1_HUMAN	ARRB1	physical	19782076
ARRB2_HUMAN	ARRB2	physical	19782076
MP2K4_HUMAN	MAP2K4	physical	12788955
GCH1_HUMAN	GCH1	physical	19294699
TF65_HUMAN	RELA	physical	21988832
TNIP1_HUMAN	TNIP1	physical	21988832
MK10_HUMAN	MAPK10	physical	23602568
MOES_HUMAN	MSN	physical	23602568
EZRI_HUMAN	EZR	physical	23602568
RADI_HUMAN	RDX	physical	23602568
WDR62_HUMAN	WDR62	physical	23602568
HAX1_HUMAN	HAX1	physical	23602568
IMDH2_HUMAN	IMPDH2	physical	23602568
DDX5_HUMAN	DDX5	physical	23602568
ATF2_HUMAN	ATF2	physical	11865055
TCPH_HUMAN	CCT7	physical	26186194
TCPW_HUMAN	CCT6B	physical	26186194
TCPB_HUMAN	CCT2	physical	26186194
DDI1_HUMAN	DDI1	physical	28514442
TCPB_HUMAN	CCT2	physical	28514442
TCPW_HUMAN	CCT6B	physical	28514442
JUN_HUMAN	JUN	physical	9596579
DUS9_HUMAN	DUSP9	physical	9596579

Drug and Disease Associations

Kegg Disease
H00606	Early infantile epileptic encephalopathy; Ohtahara syndrome
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
D10168	Tanzisertib (USAN)
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of MK10_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 SER-415 AND SER-417, ANDMASS SPECTROMETRY.	19369195 [Abstract]
"Activation of JNK3 alpha 1 requires both MKK4 and MKK7: kineticcharacterization of in vitro phosphorylated JNK3 alpha 1."; Lisnock J., Griffin P., Calaycay J., Frantz B., Parsons J.,O'Keefe S.J., LoGrasso P.; Biochemistry 39:3141-3148(2000). Cited for: PARTIAL PROTEIN SEQUENCE, REGULATION BY MAP2K4 AND MAP2K7,PHOSPHORYLATION AT THR-221 AND TYR-223, COFACTOR, AND MASSSPECTROMETRY.	10715136 [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-223, AND MASSSPECTROMETRY.	18083107 [Abstract]

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