PMADS

Id:	acc3182
Group:	2sens
Protein:	p38 MAPK
Gene Symbol:	MAPK14
Protein Id:	Q16539
Protein Name:	MK14_HUMAN
PTM:	phosphorylation
Site:	Tyr180
Site Sequence:	LARHTDDEMTGYVATRWYRAP
Disease Category:	Eye diseases
Disease:	Cataract
Disease Subtype:
Disease Cellline:	SRA 01-04
Disease Info:
Drug:	honokiol
Drug Info:	"Honokiol is a natural compound with various pharmacological properties, such as anti - inflammatory and anti - cancer effects."
Effect:	modulate
Effect Info:	"Magnolol blocks H?O?-induced apoptosis of human lens epithelial cells by inhibiting the phosphorylation of ERK1/2, p38 MAPK, JNK, Akt, and NF-κB p65."
Note:
Score:	4.0
Pubmed(PMID):	20965163
Sentence Index:	20965163_5-6
Sentence:	"Mechanistically, honokiol suppressed H(2)O(2)-induced phosphorylation of ERK1/2, p38 mitogen-activated protein kinase (MAPK), JNK and Akt. Honokiol also inhibited H(2)O(2)-induced nuclear factor-kappaB (NF-kappaB)/p65 phosphorylation and translocation in HLE cells. These results demonstrate that honokiol suppresses H(2)O(2)-induced HLE cell apoptosis via interference with the MAPKs, Akt and NF-kappaB signaling, suggesting that honokiol might have a potential effect against cataract formation."

Sequence & Structure:

MSQERPTFYRQELNKTIWEVPERYQNLSPVGSGAYGSVCAAFDTKTGLRVAVKKLSRPFQSIIHAKRTYRELRLLKHMKHENVIGLLDVFTPARSLEEFNDVYLVTHLMGADLNNIVKCQKLTDDHVQFLIYQILRGLKYIHSADIIHRDLKPSNLAVNEDCELKILDFGLARHTDDEMTGYVATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAELLTGRTLFPGTDHIDQLKLILRLVGTPGAELLKKISSESARNYIQSLTQMPKMNFANVFIGANPLAVDLLEKMLVLDSDKRITAAQALAHAYFAQYHDPDDEPVADPYDQSFESRDLLIDEWKSLTYDEVISFVPPPLDQEEMES

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
MAPK14	ARRY-797	MAP kinase p38 alpha inhibitor	3	Terminated	dilated cardiomyopathy	ClinicalTrials
MAPK14	LOSMAPIMOD	MAP kinase p38 alpha inhibitor	3	Completed	acute coronary syndrome	ClinicalTrials
MAPK14	LOSMAPIMOD	MAP kinase p38 alpha inhibitor	3	Terminated	COVID-19	ClinicalTrials
MAPK14	LOSMAPIMOD	MAP kinase p38 alpha inhibitor	3	Active, not recruiting	Facioscapulohumeral dystrophy	ClinicalTrials
MAPK14	ACUMAPIMOD	MAP kinase p38 alpha inhibitor	2	Completed	chronic obstructive pulmonary disease	ClinicalTrials ClinicalTrials
MAPK14	SEMAPIMOD	MAP kinase p38 alpha inhibitor	2	Completed	Crohn's disease	ClinicalTrials ClinicalTrials ClinicalTrials
MAPK14	PF-03715455	MAP kinase p38 alpha inhibitor	2	Terminated	chronic obstructive pulmonary disease	ClinicalTrials
MAPK14	DILMAPIMOD	MAP kinase p38 alpha inhibitor	2	Completed	chronic obstructive pulmonary disease	ClinicalTrials
MAPK14	AZD-7624	MAP kinase p38 alpha inhibitor	2	Completed	chronic obstructive pulmonary disease	ClinicalTrials
MAPK14	SEMAPIMOD	MAP kinase p38 alpha inhibitor	2	Terminated	Crohn's disease	ClinicalTrials
MAPK14	PH-797804	MAP kinase p38 alpha inhibitor	2	Completed	chronic obstructive pulmonary disease	ClinicalTrials ClinicalTrials ClinicalTrials
MAPK14	LOSMAPIMOD	MAP kinase p38 alpha inhibitor	2	Completed	chronic obstructive pulmonary disease	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
MAPK14	ARRY-797	MAP kinase p38 alpha inhibitor	2	Completed	dilated cardiomyopathy	ClinicalTrials ClinicalTrials
MAPK14	DORAMAPIMOD	MAP kinase p38 alpha inhibitor	2	Terminated	rheumatoid arthritis	ClinicalTrials
MAPK14	LOSMAPIMOD	MAP kinase p38 alpha inhibitor	2	Completed	rheumatoid arthritis	ClinicalTrials ClinicalTrials
MAPK14	BMS-582949	MAP kinase p38 alpha inhibitor	2	Completed	rheumatoid arthritis	ClinicalTrials
MAPK14	DORAMAPIMOD	MAP kinase p38 alpha inhibitor	2	Completed	psoriasis	ClinicalTrials
MAPK14	BMS-582949	MAP kinase p38 alpha inhibitor	2	Completed	psoriasis	ClinicalTrials
MAPK14	DILMAPIMOD	MAP kinase p38 alpha inhibitor	2	Completed	rheumatoid arthritis	ClinicalTrials ClinicalTrials
MAPK14	PG-760564	MAP kinase p38 alpha inhibitor	2	Completed	rheumatoid arthritis	ClinicalTrials
MAPK14	TAK-715	MAP kinase p38 alpha inhibitor	2	Completed	rheumatoid arthritis	ClinicalTrials
MAPK14	TALMAPIMOD	MAP kinase p38 alpha inhibitor	2	Completed	rheumatoid arthritis	ClinicalTrials ClinicalTrials
MAPK14	PH-797804	MAP kinase p38 alpha inhibitor	2	Completed	rheumatoid arthritis	ClinicalTrials ClinicalTrials
MAPK14	VX-702	MAP kinase p38 alpha inhibitor	2	Completed	rheumatoid arthritis	ClinicalTrials ClinicalTrials
MAPK14	DILMAPIMOD	MAP kinase p38 alpha inhibitor	2	Completed	coronary artery disease	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!

MAPK14-Ser143
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC
LUAD
LUSC	0.707
non_ccRCC
PDAC
UCEC	-0.707

MAPK14-Ser252
Cancer	Intensity
BRCA	-0.822
COAD
HGSC	2.685
ccRCC	-0.234
GBM	-0.193
HNSC	0.262
LUAD	-0.258
LUSC	-0.426
non_ccRCC	0.143
PDAC	-0.484
UCEC	-0.672

MAPK14-Ser32
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC
LUAD	-0.707
LUSC
non_ccRCC
PDAC
UCEC	0.707

MAPK14-Thr175
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.659
GBM
HNSC	-1.151
LUAD	0.492
LUSC
non_ccRCC
PDAC
UCEC

MAPK14-Thr180
Cancer	Intensity
BRCA	2.28
COAD	0.452
HGSC	-1.055
ccRCC	-0.189
GBM	-0.187
HNSC	0.188
LUAD	0.929
LUSC	0.063
non_ccRCC	-0.898
PDAC	-0.317
UCEC	-1.265

MAPK14-Thr185
Cancer	Intensity
BRCA
COAD	0.707
HGSC	-0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

MAPK14-Thr239
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.707
GBM
HNSC	0.707
LUAD
LUSC
non_ccRCC
PDAC
UCEC

MAPK14-Thr241
Cancer	Intensity
BRCA
COAD
HGSC	1.02
ccRCC	-0.978
GBM
HNSC
LUAD
LUSC	-0.042
non_ccRCC
PDAC
UCEC

MAPK14-Tyr182
Cancer	Intensity
BRCA	2.374
COAD	-0.005
HGSC	-0.861
ccRCC	0.066
GBM	1.175
HNSC	-0.22
LUAD	0.029
LUSC	-0.105
non_ccRCC	-0.927
PDAC	-0.488
UCEC	-1.039

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
T	180	P	Lung cancer/carcinoma	Phosphorylation	22348039
T	180	U	Bladder cancer	Phosphorylation	33204153

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