PMADS

Id:	acc3196
Group:	2sens
Protein:	p38alpha
Gene Symbol:	MAPK14
Protein Id:	Q16539
Protein Name:	MK14_HUMAN
PTM:	phosphorylation
Site:	Tyr182
Site Sequence:	RHTDDEMTGYVATRWYRAPEI
Disease Category:	Cancer
Disease:	Colorectal Cancer
Disease Subtype:
Disease Cellline:	HT-29
Disease Info:
Drug:	LPS
Drug Info:	"LPS, or lipopolysaccharide, is a large molecule consisting of a lipid and a polysaccharide that is a component of the outer membrane of Gram-negative bacteria."
Effect:	modulate
Effect Info:	"LPS stimulation of the TLR4/MD2 complex can activate the PI3K/AKT signaling pathway and promote the function of downstream β1 integrin, thereby enhancing the adhesion and metastatic ability of CRC cells."
Note:
Score:	4.0
Pubmed(PMID):	21363926
Sentence Index:	21363926_8-9
Sentence:	"No differences were apparent in phosphorylation of p38 and MAPK isoforms, but in metastatic CRC cells expressing surface TLR4 treatment with LPS increased Ser473 phosphorylation of AKT kinase. We showed that enhanced adherence elicited by LPS in these cells could be blocked at three different levels, using Eritoran (TLR4 small molecule antagonist), PI-103 (PI3K inhibitor), or anti-beta1 integrin blocking antibodies."

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

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
Y	182	D	Breast cancer/tumor/carcinoma	Phosphorylation	23771849
Y	182	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