PMADS

Id:	acc0583
Group:	1sens
Protein:	EphA2
Gene Symbol:	EPHA2
Protein Id:	P29317
Protein Name:	EPHA2_HUMAN
PTM:	phosphorylation
Site:	Ser897
Site Sequence:	DPRVSIRLPSTSGSEGVPFRT
Disease Category:	Cancer
Disease:	Ovarian Cancer
Disease Subtype:	high-grade serous ovarian cancer
Disease Cellline:	OVCAR8
Disease Info:
Drug:	platinum
Drug Info:	"Cisplatin: A platinum-containing chemotherapeutic agent used in the treatment of various cancers, including testicular, ovarian, and lung cancers, by forming DNA adducts that inhibit cancer cell replication. Carboplatin: A second-generation platinum-based antineoplastic drug with reduced nephrotoxicity compared to cisplatin, commonly employed in ovarian cancer and other malignancies. Oxaliplatin: A third-generation platinum compound effective against colorectal cancer, characterized by its distinct mechanism of action and reduced cross-resistance with other platinum drugs. "
Effect:	inhibit
Effect Info:	"RSK inhibitors can restore the phosphorylation of Y588 by inhibiting the phosphorylation of S897 in EphA2, thereby enhancing the therapeutic effect of cisplatin."
Note:
Score:	5.0
Pubmed(PMID):	32115889
Sentence Index:	32115889_4
Sentence:	"Mechanistically, pharmacological inhibition or knockdown of RSK1/2 prevented oncogenic EphA2-S897 phosphorylation and EphA2-GPRC5A co-regulation, thereby facilitating a signaling shift to the canonical tumor-suppressive tyrosine phosphorylation and consequent downregulation of EphA2."

Sequence & Structure:

MELQAARACFALLWGCALAAAAAAQGKEVVLLDFAAAGGELGWLTHPYGKGWDLMQNIMNDMPIYMYSVCNVMSGDQDNWLRTNWVYRGEAERIFIELKFTVRDCNSFPGGASSCKETFNLYYAESDLDYGTNFQKRLFTKIDTIAPDEITVSSDFEARHVKLNVEERSVGPLTRKGFYLAFQDIGACVALLSVRVYYKKCPELLQGLAHFPETIAGSDAPSLATVAGTCVDHAVVPPGGEEPRMHCAVDGEWLVPIGQCLCQAGYEKVEDACQACSPGFFKFEASESPCLECPEHTLPSPEGATSCECEEGFFRAPQDPASMPCTRPPSAPHYLTAVGMGAKVELRWTPPQDSGGREDIVYSVTCEQCWPESGECGPCEASVRYSEPPHGLTRTSVTVSDLEPHMNYTFTVEARNGVSGLVTSRSFRTASVSINQTEPPKVRLEGRSTTSLSVSWSIPPPQQSRVWKYEVTYRKKGDSNSYNVRRTEGFSVTLDDLAPDTTYLVQVQALTQEGQGAGSKVHEFQTLSPEGSGNLAVIGGVAVGVVLLLVLAGVGFFIHRRRKNQRARQSPEDVYFSKSEQLKPLKTYVDPHTYEDPNQAVLKFTTEIHPSCVTRQKVIGAGEFGEVYKGMLKTSSGKKEVPVAIKTLKAGYTEKQRVDFLGEAGIMGQFSHHNIIRLEGVISKYKPMMIITEYMENGALDKFLREKDGEFSVLQLVGMLRGIAAGMKYLANMNYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDDPEATYTTSGGKIPIRWTAPEAISYRKFTSASDVWSFGIVMWEVMTYGERPYWELSNHEVMKAINDGFRLPTPMDCPSAIYQLMMQCWQQERARRPKFADIVSILDKLIRAPDSLKTLADFDPRVSIRLPSTSGSEGVPFRTVSEWLESIKMQQYTEHFMAAGYTAIEKVVQMTNDDIKRIGVRLPGHQKRIAYSLLGLKDQVNTVGIPI

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
EPHA2	DASATINIB	Ephrin type-A receptor 2 inhibitor	4	Unknown status	acute lymphoblastic leukemia	ClinicalTrials
EPHA2	DASATINIB	Ephrin type-A receptor 2 inhibitor	4	-	acute lymphoblastic leukemia	DailyMed DailyMed
EPHA2	DASATINIB	Ephrin type-A receptor 2 inhibitor	4	-	chronic myelogenous leukemia	DailyMed DailyMed
EPHA2	DASATINIB	Ephrin type-A receptor 2 inhibitor	4	Completed	chronic myelogenous leukemia	ClinicalTrials ClinicalTrials
EPHA2	DASATINIB	Ephrin type-A receptor 2 inhibitor	4	Recruiting	chronic myelogenous leukemia	ClinicalTrials ClinicalTrials ClinicalTrials
EPHA2	DASATINIB	Ephrin type-A receptor 2 inhibitor	4	Unknown status	chronic myelogenous leukemia	ClinicalTrials
EPHA2	DASATINIB	Ephrin type-A receptor 2 inhibitor	4	-	neoplasm	ATC
EPHA2	REGORAFENIB	Ephrin type-A receptor 2	4	-	neoplasm	ATC
EPHA2	VANDETANIB	Ephrin receptor inhibitor	4	-	neoplasm	ATC
EPHA2	VANDETANIB	Ephrin receptor inhibitor	4	-	thyroid carcinoma	DailyMed
EPHA2	VANDETANIB	Ephrin receptor inhibitor	4	-	thyroid neoplasm	EMA
EPHA2	REGORAFENIB	Ephrin type-A receptor 2	4	-	colorectal neoplasm	EMA
EPHA2	DASATINIB	Ephrin type-A receptor 2 inhibitor	4	-	lymphoid leukemia	EMA
EPHA2	DASATINIB	Ephrin type-A receptor 2 inhibitor	4	-	Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive	EMA
EPHA2	VANDETANIB	Ephrin receptor inhibitor	4	Active, not recruiting	thyroid cancer	ClinicalTrials
EPHA2	VANDETANIB	Ephrin receptor inhibitor	4	-	medullary thyroid gland carcinoma	DailyMed
EPHA2	REGORAFENIB	Ephrin type-A receptor 2	3	Recruiting	hepatocellular carcinoma	ClinicalTrials
EPHA2	REGORAFENIB	Ephrin type-A receptor 2	3	Terminated	hepatocellular carcinoma	ClinicalTrials
EPHA2	REGORAFENIB	Ephrin type-A receptor 2	3	Completed	hepatocellular carcinoma	ClinicalTrials
EPHA2	DASATINIB	Ephrin type-A receptor 2 inhibitor	3	Completed	acute lymphoblastic leukemia	ClinicalTrials ClinicalTrials
EPHA2	DASATINIB	Ephrin type-A receptor 2 inhibitor	3	Completed	acute myeloid leukemia	ClinicalTrials
EPHA2	DASATINIB	Ephrin type-A receptor 2 inhibitor	3	Active, not recruiting	acute lymphoblastic leukemia	ClinicalTrials
EPHA2	DASATINIB	Ephrin type-A receptor 2 inhibitor	3	Not yet recruiting	acute lymphoblastic leukemia	ClinicalTrials
EPHA2	DASATINIB	Ephrin type-A receptor 2 inhibitor	3	Terminated	chronic myelogenous leukemia	ClinicalTrials
EPHA2	DASATINIB	Ephrin type-A receptor 2 inhibitor	3	Active, not recruiting	chronic myelogenous 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!

EPHA2-Ser516
Cancer	Intensity
BRCA
COAD
HGSC	1.828
ccRCC	0.406
GBM
HNSC
LUAD	-0.525
LUSC	-0.679
non_ccRCC	-0.852
PDAC	-0.177
UCEC

EPHA2-Ser838
Cancer	Intensity
BRCA
COAD
HGSC	1.368
ccRCC	-0.754
GBM	-1.001
HNSC
LUAD
LUSC	0.769
non_ccRCC	-1.021
PDAC	0.919
UCEC	-0.28

EPHA2-Ser843
Cancer	Intensity
BRCA
COAD
HGSC	1.069
ccRCC	-0.155
GBM	-0.913
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

EPHA2-Ser845
Cancer	Intensity
BRCA
COAD	-1.151
HGSC
ccRCC	0.66
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	0.491

EPHA2-Ser847
Cancer	Intensity
BRCA
COAD	-0.72
HGSC
ccRCC	0.912
GBM	-0.309
HNSC
LUAD
LUSC	-1.491
non_ccRCC	1.471
PDAC	-0.212
UCEC	0.349

EPHA2-Thr844
Cancer	Intensity
BRCA
COAD
HGSC	0.707
ccRCC	-0.707
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

EPHA2-Tyr521
Cancer	Intensity
BRCA
COAD	-0.304
HGSC
ccRCC
GBM	-0.476
HNSC
LUAD	1.684
LUSC	-0.255
non_ccRCC	-1.21
PDAC	0.561
UCEC

EPHA2-Tyr540
Cancer	Intensity
BRCA
COAD
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC	-0.707
PDAC
UCEC

EPHA2-Tyr718
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
S	897	D	Ewing sarcoma	Phosphorylation	36394520
S	897	P	Cancer	Phosphorylation	35668076
S	897	U	Breast cancer	Phosphorylation	23772378
S	897	U	Cervical cancer/carcinoma	Phosphorylation	23772378
S	897	U	Lung cancer	Phosphorylation	26158630
S	897	U	Glioblastoma	Phosphorylation	19573808 ; 35124461
S	897	U	Thyroid cancer	Phosphorylation	32762307
S	897	U	Hepatocellular carcinoma	Phosphorylation	34484860

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

Protein	Gene	PTM	Position	Modified sequence	Cell	Drug	pEC50	Regulation
P29317	EPHA2	P	Ser897;Ser901	LPS(ph)TSGS(ph)EGVPFR	A431	Imatinib	5.191	up
P29317	EPHA2	P	Ser892;Ser897	VS(ph)IRLPS(ph)TSGSEGVPFR	A431	Gefitinib	6.4271	down
P29317	EPHA2	P	Ser897;Ser901	LPS(ph)TSGS(ph)EGVPFR	A431	Dasatinib	5.5339	down
P29317	EPHA2	P	Ser897;Ser901	LPS(ph)TSGS(ph)EGVPFR	A431	Gefitinib	6.8186	down
P29317	EPHA2	P	Ser892;Ser897	VS(ph)IRLPS(ph)TSGSEGVPFR	A431	Gefitinib	6.6849	down
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A431	Gefitinib	6.4768	down
P29317	EPHA2	P	Ser897;Ser901	LPS(ph)TSGS(ph)EGVPFR	A431	Gefitinib	7.0733	down
P29317	EPHA2	P	Ser892;Ser897	VS(ph)IRLPS(ph)TSGSEGVPFR	A431	Gefitinib	6.8432	down
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A431	Gefitinib	6.6526	down
P29317	EPHA2	P	Ser897;Ser901	LPS(ph)TSGS(ph)EGVPFR	A431	Gefitinib	6.5536	down
P29317	EPHA2	P	Ser892;Ser897	VS(ph)IRLPS(ph)TSGSEGVPFR	A431	Afatinib	8.0916	down
P29317	EPHA2	P	Ser897	VSIRLPS(ph)TSGSEGVPFR	A549	PD325901	9.9212	down
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A549	PD325901	9.3521	down
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A549	PD325901	9.3067	down
P29317	EPHA2	P	Ser897;Ser901	LPS(ph)TSGS(ph)EGVPFR	KYSE-520	SHP099	6.204	down
P29317	EPHA2	P	Ser897;Ser899	LPS(ph)TS(ph)GSEGVPFR	KYSE-520	SHP099	6.1719	down
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	PC-9	GeftinibAZD4547-1to80	8.2736	down
P29317	EPHA2	P	Ser897;Ser901	LPS(ph)TSGS(ph)EGVPFR	A431	Afatinib	8.127	down
P29317	EPHA2	P	Ser897;Ser901	LPS(ph)TSGS(ph)EGVPFR	A431	Afatinib	8.2913	down
P29317	EPHA2	P	Ser892;Ser897	VS(ph)IRLPS(ph)TSGSEGVPFR	A431	Dasatinib	5.4042	down
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A431	Afatinib	8.3227	down
P29317	EPHA2	P	Ser892;Ser897	VS(ph)IRLPS(ph)TSGSEGVPFR	A431	Afatinib	8.3121	down
P29317	EPHA2	P	Ser892;Ser897	VS(ph)IRLPS(ph)TSGSEGVPFR	A431	Afatinib	8.0842	down
P29317	EPHA2	P	Ser897;Ser901	LPS(ph)TSGS(ph)EGVPFR	A431	Afatinib	8.1981	down
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A431	Afatinib	8.0054	down
P29317	EPHA2	P	Ser897;Ser901	LPS(ph)TSGS(ph)EGVPFR	A431	Dasatinib	6.2104	down
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A431	Dasatinib	5.4597	down
P29317	EPHA2	P	Ser892;Ser897	VS(ph)IRLPS(ph)TSGSEGVPFR	A431	Dasatinib	5.7212	down
P29317	EPHA2	P	Ser897;Ser899	LPS(ph)TS(ph)GSEGVPFR	A431	Dasatinib	5.4249	down
P29317	EPHA2	P	Ser897;Ser901	LPS(ph)TSGS(ph)EGVPFR	A431	Afatinib	8.4026	down
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A431	Afatinib	8.471	down
P29317	EPHA2	P	Ser897;Ser901	LPS(ph)TSGS(ph)EGVPFR	A431	Dasatinib	5.5987	down
P29317	EPHA2	P	Ser897	VSIRLPS(ph)TSGSEGVPFR	A549	MK2206	7.2309	-
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A549	MK2206	5.5588	-
P29317	EPHA2	P	Ser897;Ser901	LPS(ph)TSGS(ph)EGVPFR	A549	Nintedanib	2.5603	-
P29317	EPHA2	P	Ser892;Ser897	VS(ph)IRLPS(ph)TSGSEGVPFR	A549	Dactolisib	7.8301	-
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	PC-9	AZD4547	8.649	-
P29317	EPHA2	P	Ser892;Ser897	VS(ph)IRLPS(ph)TSGSEGVPFR	A549	PD325901	6.2889	-
P29317	EPHA2	P	Ser892;Ser897	VS(ph)IRLPS(ph)TSGSEGVPFR	A549	Pictilisib	8.7602	-
P29317	EPHA2	P	Ser897;Ser901	LPS(ph)TSGS(ph)EGVPFR	A549	Pictilisib	8.7369	-
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A549	Pictilisib	5.2639	-
P29317	EPHA2	P	Ser892;Ser897	VS(ph)IRLPS(ph)TSGSEGVPFR	A549	Refametinib	6.1825	-
P29317	EPHA2	P	Ser892;Ser897;Thr898	VS(ph)IRLPS(ph)T(ph)SGSEGVPFR	A549	Tideglusib	14.9369	-
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A549	Tideglusib	11.1364	-
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	KYSE-520	SHP099	6.5212	-
P29317	EPHA2	P	Ser897;Ser901	LPS(ph)TSGS(ph)EGVPFR	A549	Tideglusib	10.7173	-
P29317	EPHA2	P	Ser892;Ser897	VS(ph)IRLPS(ph)TSGSEGVPFR	A549	Tideglusib	6.2329	-
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A459	SelumetinibMK2206-3to1	5.9772	-
P29317	EPHA2	P	Ser897;Ser899;Ser901	LPS(ph)TS(ph)GS(ph)EGVPFR	A431	Dasatinib	9.2368	-
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A431	Dasatinib	7.2469	-
P29317	EPHA2	P	Ser897;Ser901	LPS(ph)TSGS(ph)EGVPFR	A431	Dasatinib	7.1533	-
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A431	Dasatinib	5.4592	-
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A431	Dasatinib	5.7589	-
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A431	Dasatinib	6.2243	-
P29317	EPHA2	P	Ser897;Ser901	LPS(ph)TSGS(ph)EGVPFR	A431	Gefitinib	6.459	-
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A459	MK2206	14.5229	-
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A459	MK2206	9.6886	-
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A459	Selumetinib	7.7635	-
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A549	Dasatinib	4.7232	-
P29317	EPHA2	P	Ser897;Ser901	LPS(ph)TSGS(ph)EGVPFR	A549	AZD8055	8.5071	-
P29317	EPHA2	P	Ser892;Ser897	VS(ph)IRLPS(ph)TSGSEGVPFR	A549	AZD8055	8.2095	-
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A549	AZD8055	7.7847	-
P29317	EPHA2	P	Ser897;Ser899	VSIRLPS(ph)TS(ph)GSEGVPFR	A549	Dactolisib	10.4773	-
P29317	EPHA2	P	Ser897;Ser901	VSIRLPS(ph)TSGS(ph)EGVPFR	A549	Dactolisib	8.3469	-
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A549	Dactolisib	7.0113	-
P29317	EPHA2	P	Ser897	LPS(ph)TSGSEGVPFR	A549	Dasatinib	8.5932	-
P29317	EPHA2	P	Ser897	VSIRLPS(ph)TSGSEGVPFR	A549	Dasatinib	8.35	-
P29317	EPHA2	P	Ser897;Ser901	LPS(ph)TSGS(ph)EGVPFR	A549	Dasatinib	5.739	-

pEC50 Note: pEC50 is the negative logarithm of EC50 (half-maximal effective concentration, dosage unit Mol), calculated as pEC50 = -log10(EC50), which quantifies the potency of a drug or compound.

Function score:

source: funscoR

No data.

Cross Links:

CTD
DMRdb