PMADS

Id:	acc0244
Group:	2sens
Protein:	JNK
Gene Symbol:	MAPK8
Protein Id:	P45983
Protein Name:	MK08_HUMAN
PTM:	phosphorylation
Site:	Thr185
Site Sequence:	AGTSFMMTPYVVTRYYRAPEV
Disease Category:	Cancer
Disease:	Renal Cancer
Disease Subtype:
Disease Cellline:	A489
Disease Info:
Drug:	NSC-743380
Drug Info:	-
Effect:	modulate
Effect Info:	NSC - 743380 exhibits potent antitumor activity by activating the phosphorylation of JNK and ERK and inhibiting the phosphorylation of JAK2/STAT3.
Note:
Score:	4.0
Pubmed(PMID):	22174819
Sentence Index:	22174819_12-13
Sentence:	"Mechanistic characterization revealed that NSC-743380 suppressed the phosphorylation of C-terminal domain of RNA polymerase II, induced JNK activation, inhibited JAK2/STAT3 phosphorylation and suppressed cyclin D1 expression in sensitive human cancer cells. Blocking JNK activation or overexpression of constitutively active STAT3 partially blocked NSC-743380-induced antitumor activity."

Sequence & Structure:

MSRSKRDNNFYSVEIGDSTFTVLKRYQNLKPIGSGAQGIVCAAYDAILERNVAIKKLSRPFQNQTHAKRAYRELVLMKCVNHKNIIGLLNVFTPQKSLEEFQDVYIVMELMDANLCQVIQMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMMTPYVVTRYYRAPEVILGMGYKENVDLWSVGCIMGEMVCHKILFPGRDYIDQWNKVIEQLGTPCPEFMKKLQPTVRTYVENRPKYAGYSFEKLFPDVLFPADSEHNKLKASQARDLLSKMLVIDASKRISVDEALQHPYINVWYDPSEAEAPPPKIPDKQLDEREHTIEEWKELIYKEVMDLEERTKNGVIRGQPSPLGAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAAGPLGCCR

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
MAPK8	BENTAMAPIMOD	c-Jun N-terminal kinase, JNK inhibitor	2	Completed	endometriosis	ClinicalTrials
MAPK8	TANZISERTIB	c-Jun N-terminal kinase 1 inhibitor	2	Terminated	idiopathic pulmonary fibrosis	ClinicalTrials
MAPK8	TANZISERTIB	c-Jun N-terminal kinase 1 inhibitor	2	Terminated	lupus erythematosus	ClinicalTrials
MAPK8	CC-401	c-Jun N-terminal kinase 1 inhibitor	1	Terminated	myeloid leukemia	ClinicalTrials

Note: Only show clinically investigational or approved drugs with protein targets.

Protein Tractability:

source: Open Targets

Small molecule

Antibody

PROTAC

Other modalities

Approved Drug

Advanced Clinical

Phase 1 Clinical

Structure with Ligand

High-Quality Ligand

High-Quality Pocket

Med-Quality Pocket

Druggable Family

Approved Drug

Advanced Clinical

Phase 1 Clinical

UniProt loc high conf

GO CC high conf

UniProt loc med conf

UniProt SigP or TMHMM

GO CC med conf

Human Protein Atlas loc

Approved Drug

Advanced Clinical

Phase 1 Clinical

Literature

UniProt Ubiquitination

Database Ubiquitination

Half-life Data

Small Molecule Binder

Approved Drug

Advanced Clinical

Phase 1 Clinical

PTM Intensity:

source: CPTAC

No intensity data of this site,
show all other sites!

MAPK8-Ser301
Cancer	Intensity
BRCA
COAD	0.707
HGSC	-0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

MAPK8-Thr183
Cancer	Intensity
BRCA
COAD	0.707
HGSC	-0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

MAPK8-Tyr185
Cancer	Intensity
BRCA
COAD	-0.707
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

MAPK8IP2-Ser250
Cancer	Intensity
BRCA	-0.707
COAD
HGSC
ccRCC
GBM	0.707
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

MAPK8IP2-Ser251
Cancer	Intensity
BRCA	-0.707
COAD
HGSC
ccRCC
GBM	0.707
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

MAPK8IP2-Ser254
Cancer	Intensity
BRCA	-0.707
COAD
HGSC
ccRCC
GBM	0.707
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

MAPK8IP3-Ser207
Cancer	Intensity
BRCA
COAD
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC	-0.707
UCEC

MAPK8IP3-Ser365
Cancer	Intensity
BRCA
COAD	1.014
HGSC	-1.48
ccRCC	-0.292
GBM	-0.5
HNSC
LUAD
LUSC	1.549
non_ccRCC
PDAC	-0.198
UCEC	-0.092

MAPK8IP3-Ser579
Cancer	Intensity
BRCA
COAD	-0.237
HGSC	0.319
ccRCC
GBM
HNSC
LUAD	-1.233
LUSC
non_ccRCC	1.15
PDAC
UCEC

MAPK8IP3-Ser596
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.707
GBM
HNSC
LUAD
LUSC
non_ccRCC	0.707
PDAC
UCEC

MAPK8IP3-Ser670
Cancer	Intensity
BRCA	1.002
COAD
HGSC
ccRCC
GBM	-0.998
HNSC
LUAD	-0.004
LUSC
non_ccRCC
PDAC
UCEC

MAPK8IP3-Thr275
Cancer	Intensity
BRCA
COAD	0.746
HGSC	-1.136
ccRCC
GBM	0.39
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
Y	185	U	Pancreatic cancer	Phosphorylation	37016317
Y	185	U	Type 2 diabetes	Phosphorylation	21931634

State Note: Based on the distinct PTM states in diseases, PTMD classified all disease-associated PTMs into six classes, including whether the up-regulation (U) or down-regulation (D) of PTM levels, the absence (A) or presence (P) of PTMs, and the creation (C) or disruption (N) of PTM sites are associated with diseases.

PTM-Drug Perturbation Response:

source: DecryptM

No data.

Function score:

source: funscoR

No data.

Cross Links:

CTD
DMRdb