PMADS

Id:	acc2043
Group:	2sens
Protein:	MEK2
Gene Symbol:	MAP2K2
Protein Id:	P36507
Protein Name:	MP2K2_HUMAN
PTM:	phosphorylation
Site:	Ser221
Site Sequence:	DFGVSGQLIDSMANSFVGTRS
Disease Category:	Cancer
Disease:	Breast Cancer
Disease Subtype:
Disease Cellline:	MCF7
Disease Info:
Drug:	DHA
Drug Info:	-
Effect:	modulate
Effect Info:	DHA induces apoptosis in human breast cancer cells (MCF - 7 and SK - BR - 3) and mouse mammary tissues by inhibiting the action of SDC - 1 in the MEK - Erk signaling pathway.
Note:
Score:	4.0
Pubmed(PMID):	21771724
Sentence Index:	21771724_8-9
Sentence:	"Phosphorylation of MEK, Erk and Bad was lower in the Fat-1 versus wt tissue and (ii) SDC-1(-/-) mice that demonstrated markedly higher levels of phosphorylated MEK, Erk and Bad in mammary gland tissue compared with those of SDC(+/+) mice. These data elucidate a pathway whereby SDC-1, upregulated by DHA, induces apoptosis in breast cancer cells through inhibition of MEK/Erk/Bad signaling."

Sequence & Structure:

MLARRKPVLPALTINPTIAEGPSPTSEGASEANLVDLQKKLEELELDEQQKKRLEAFLTQKAKVGELKDDDFERISELGAGNGGVVTKVQHRPSGLIMARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKEAKRIPEEILGKVSIAVLRGLAYLREKHQIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMAPERLQGTHYSVQSDIWSMGLSLVELAVGRYPIPPPDAKELEAIFGRPVVDGEEGEPHSISPRPRPPGRPVSGHGMDSRPAMAIFELLDYIVNEPPPKLPNGVFTPDFQEFVNKCLIKNPAERADLKMLTNHTFIKRSEVEEVDFAGWLCKTLRLNQPGTPTRTAV

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
MAP2K2	COBIMETINIB	Dual specificity mitogen-activated protein kinase kinase 2 inhibitor	4	-	neoplasm	ATC
MAP2K2	SELUMETINIB	Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor	4	-	neoplasm	ATC
MAP2K2	BINIMETINIB	Dual specificity mitogen-activated protein kinase kinase 2 inhibitor	4	-	neoplasm	ATC
MAP2K2	BINIMETINIB	Dual specificity mitogen-activated protein kinase kinase 2 inhibitor	4	Recruiting	neoplasm	ClinicalTrials
MAP2K2	COBIMETINIB FUMARATE	Dual specificity mitogen-activated protein kinase kinase 2 inhibitor	4	-	melanoma	EMA
MAP2K2	BINIMETINIB	Dual specificity mitogen-activated protein kinase kinase 2 inhibitor	4	-	melanoma	DailyMed EMA
MAP2K2	COBIMETINIB FUMARATE	Dual specificity mitogen-activated protein kinase kinase 2 inhibitor	4	-	metastatic melanoma	DailyMed
MAP2K2	BINIMETINIB	Dual specificity mitogen-activated protein kinase kinase 2 inhibitor	4	-	metastatic melanoma	FDA
MAP2K2	TRAMETINIB DIMETHYL SULFOXIDE	Dual specificity mitogen-activated protein kinase kinase 2 inhibitor	4	-	metastatic melanoma	FDA
MAP2K2	SELUMETINIB SULFATE	Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor	4	-	neurofibromatosis	DailyMed
MAP2K2	TRAMETINIB DIMETHYL SULFOXIDE	Dual specificity mitogen-activated protein kinase kinase 2 inhibitor	4	-	thyroid cancer	DailyMed
MAP2K2	TRAMETINIB DIMETHYL SULFOXIDE	Dual specificity mitogen-activated protein kinase kinase 2 inhibitor	4	-	lung cancer	DailyMed
MAP2K2	SELUMETINIB SULFATE	Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor	4	-	neurofibromatosis type 1	FDA EMA
MAP2K2	SELUMETINIB	Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor	3	Recruiting	astrocytoma	ClinicalTrials
MAP2K2	SELUMETINIB SULFATE	Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor	3	Recruiting	astrocytoma	ClinicalTrials
MAP2K2	BINIMETINIB	Dual specificity mitogen-activated protein kinase kinase 2 inhibitor	3	Completed	cutaneous melanoma	ClinicalTrials
MAP2K2	COBIMETINIB	Dual specificity mitogen-activated protein kinase kinase 2 inhibitor	3	Active, not recruiting	melanoma	ClinicalTrials
MAP2K2	COBIMETINIB	Dual specificity mitogen-activated protein kinase kinase 2 inhibitor	3	Completed	melanoma	ClinicalTrials
MAP2K2	COBIMETINIB	Dual specificity mitogen-activated protein kinase kinase 2 inhibitor	3	Terminated	melanoma	ClinicalTrials
MAP2K2	COBIMETINIB	Dual specificity mitogen-activated protein kinase kinase 2 inhibitor	3	Withdrawn	melanoma	ClinicalTrials
MAP2K2	BINIMETINIB	Dual specificity mitogen-activated protein kinase kinase 2 inhibitor	3	Active, not recruiting	melanoma	ClinicalTrials ClinicalTrials ClinicalTrials
MAP2K2	TRAMETINIB	Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor	3	Recruiting	melanoma	ClinicalTrials ClinicalTrials
MAP2K2	TRAMETINIB	Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor	3	Active, not recruiting	melanoma	ClinicalTrials
MAP2K2	TRAMETINIB	Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor	3	Completed	melanoma	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
MAP2K2	SELUMETINIB	Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor	3	Active, not recruiting	non-small cell lung carcinoma	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!

MAP2K2-Ser216
Cancer	Intensity
BRCA
COAD	0.332
HGSC	-2.654
ccRCC	0.205
GBM	0.498
HNSC	0.468
LUAD	0.344
LUSC	0.315
non_ccRCC	0.259
PDAC
UCEC	0.233

MAP2K2-Ser222
Cancer	Intensity
BRCA	1.103
COAD	0.207
HGSC	-2.178
ccRCC	-0.277
GBM	-0.734
HNSC	1.342
LUAD	0.555
LUSC	0.176
non_ccRCC	-0.246
PDAC	-0.741
UCEC	0.793

MAP2K2-Ser226
Cancer	Intensity
BRCA	1.866
COAD	-0.038
HGSC	-2.106
ccRCC	-0.217
GBM	0.298
HNSC	0.845
LUAD	0.102
LUSC	0.712
non_ccRCC	-0.524
PDAC	-0.441
UCEC	-0.496

MAP2K2-Ser23
Cancer	Intensity
BRCA
COAD	-0.187
HGSC	-1.963
ccRCC	0.835
GBM	0.513
HNSC	0.273
LUAD
LUSC
non_ccRCC	0.949
PDAC	-0.419
UCEC

MAP2K2-Ser26
Cancer	Intensity
BRCA
COAD	-0.238
HGSC
ccRCC	1.223
GBM	-1.454
HNSC	-0.101
LUAD	0.57
LUSC
non_ccRCC
PDAC
UCEC

MAP2K2-Ser30
Cancer	Intensity
BRCA
COAD	0.707
HGSC
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC	-0.707
UCEC

MAP2K2-Ser76
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.895
GBM	-1.08
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	0.185

MAP2K2-Thr17
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.707
GBM
HNSC
LUAD	0.707
LUSC
non_ccRCC
PDAC
UCEC

MAP2K2-Thr25
Cancer	Intensity
BRCA
COAD	-0.451
HGSC
ccRCC	0.234
GBM	1.524
HNSC	-1.184
LUAD	-0.123
LUSC
non_ccRCC
PDAC
UCEC

MAP2K2-Thr394
Cancer	Intensity
BRCA	-0.026
COAD
HGSC	2.485
ccRCC	-0.291
GBM	-0.696
HNSC	0.064
LUAD	0.242
LUSC	0.231
non_ccRCC	-0.063
PDAC	-0.625
UCEC	-1.321

MAP2K2-Thr396
Cancer	Intensity
BRCA
COAD	-0.707
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
T	394	U	Breast cancer	Phosphorylation	33226073
-	-	U	Breast cancer	Phosphorylation	15193230
K	48	U	Hepatocellular carcinoma	Ubiquitination	29706623

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