PMADS

Id:	acc1650
Group:	2sens_supp
Protein:	eIF2alpha
Gene Symbol:	EIF2A
Protein Id:	Q9BY44
Protein Name:	EIF2A_HUMAN
PTM:	phosphorylation
Site:	Ser51
Site Sequence:	CIFSKDGTLFAWGNGEKVNII
Disease Category:	Cancer
Disease:	Lung Cancer
Disease Subtype:	NSCLC
Disease Cellline:	A549
Disease Info:
Drug:	doxorubicin
Drug Info:	"Doxorubicin is a cytotoxic anthracycline antibiotic and anticancer chemotherapeutic agent that inhibits human DNA topoisomerase I and II with IC50 values of 0.8 μM and 2.67 μM, respectively, and induces apoptosis and autophagy."
Effect:	negative
Effect Info:	"Doxorubicin treatment can lead to an increase in eIF2 phosphorylation, and this eIF2 phosphorylation promotes the migration of tumor cells to a certain extent; the combined use of ISRIB or trazodone to inhibit eIF2 phosphorylation can suppress tumor migration and metastasis."
Note:
Score:	5.0
Pubmed(PMID):	31848319
Sentence Index:	31848319_5-6
Sentence:	"Doxorubicin inhibited the multiprotein complex mTORC1, which led to the phosphorylation of the translation factor eIF2alpha. We showed that eIF2alpha phosphorylation did not inhibit protein synthesis but was instead required for cell migration and that pharmacologically blocking this pathway with either ISRIB or trazodone limited cell migration. These results support the notion that therapeutic targeting of eIF2alpha signaling could restrict tumor cell metastasis and invasion and could be beneficial to subsets of patients with cancer."

Sequence & Structure:

MAPSTPLLTVRGSEGLYMVNGPPHFTESTVFPRESGKNCKVCIFSKDGTLFAWGNGEKVNIISVTNKGLLHSFDLLKAVCLEFSPKNTVLATWQPYTTSKDGTAGIPNLQLYDVKTGTCLKSFIQKKMQNWCPSWSEDETLCARNVNNEVHFFENNNFNTIANKLHLQKINDFVLSPGPQPYKVAVYVPGSKGAPSFVRLYQYPNFAGPHAALANKSFFKADKVTMLWNKKATAVLVIASTDVDKTGASYYGEQTLHYIATNGESAVVQLPKNGPIYDVVWNSSSTEFCAVYGFMPAKATIFNLKCDPVFDFGTGPRNAAYYSPHGHILVLAGFGNLRGQMEVWDVKNYKLISKPVASDSTYFAWCPDGEHILTATCAPRLRVNNGYKIWHYTGSILHKYDVPSNAELWQVSWQPFLDGIFPAKTITYQAVPSEVPNEEPKVATAYRPPALRNKPITNSKLHEEEPPQNMKPQSGNDKPLSKTALKNQRKHEAKKAAKQEARSDKSPDLAPTPAPQSTPRNTVSQSISGDPEIDKKIKNLKKKLKAIEQLKEQAATGKQLEKNQLEKIQKETALLQELEDLELGI

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

No data.

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!

EIF2A-Ser481
Cancer	Intensity
BRCA	0.254
COAD	-1.143
HGSC	1.978
ccRCC	0.421
GBM	-0.483
HNSC	0.059
LUAD	-1.003
LUSC	-1.463
non_ccRCC	1.047
PDAC	0.224
UCEC	0.108

EIF2A-Ser501
Cancer	Intensity
BRCA	0.096
COAD	0.065
HGSC	2.656
ccRCC	-0.628
GBM	-0.4
HNSC	-0.228
LUAD	-0.676
LUSC
non_ccRCC	-0.5
PDAC	0.33
UCEC	-0.715

EIF2A-Ser503
Cancer	Intensity
BRCA
COAD	-1.132
HGSC	1.288
ccRCC	-0.657
GBM
HNSC
LUAD
LUSC	-0.842
non_ccRCC
PDAC	0.76
UCEC	0.584

EIF2A-Thr487
Cancer	Intensity
BRCA
COAD	-0.905
HGSC	-0.168
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	1.073

EIF2AK1-Ser257
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	-0.294
HNSC	1.036
LUAD	-0.623
LUSC	-1.165
non_ccRCC
PDAC
UCEC	1.046

EIF2AK1-Ser294
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	1.069
HNSC	-0.751
LUAD
LUSC	-0.948
non_ccRCC
PDAC
UCEC	0.629

EIF2AK2-Ser167
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC	0.707
LUAD	-0.707
LUSC
non_ccRCC
PDAC
UCEC

EIF2AK2-Ser171
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC	-0.707
LUAD
LUSC
non_ccRCC
PDAC
UCEC	0.707

EIF2AK2-Ser33
Cancer	Intensity
BRCA
COAD
HGSC	-0.707
ccRCC
GBM
HNSC
LUAD
LUSC	0.707
non_ccRCC
PDAC
UCEC

EIF2AK2-Ser83
Cancer	Intensity
BRCA	-0.012
COAD	-0.018
HGSC	-0.58
ccRCC
GBM	1.525
HNSC	-1.437
LUAD
LUSC	0.522
non_ccRCC
PDAC
UCEC

EIF2AK2-Ser92
Cancer	Intensity
BRCA
COAD
HGSC	-1.155
ccRCC	0.586
GBM
HNSC
LUAD	0.569
LUSC
non_ccRCC
PDAC
UCEC

EIF2AK2-Ser93
Cancer	Intensity
BRCA
COAD	0.953
HGSC	-1.041
ccRCC
GBM
HNSC	0.088
LUAD
LUSC
non_ccRCC
PDAC
UCEC

EIF2AK2-Thr170
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC	0.707
LUAD	-0.707
LUSC
non_ccRCC
PDAC
UCEC

EIF2AK3-Ser404
Cancer	Intensity
BRCA	-1.974
COAD
HGSC	1.579
ccRCC	0.387
GBM	0.07
HNSC	0.184
LUAD	0.272
LUSC	-0.245
non_ccRCC	0.654
PDAC	-0.928
UCEC

EIF2AK3-Ser537
Cancer	Intensity
BRCA	-0.088
COAD
HGSC
ccRCC
GBM
HNSC
LUAD	1.35
LUSC	-1.063
non_ccRCC
PDAC	-0.199
UCEC

EIF2AK3-Ser564
Cancer	Intensity
BRCA	-0.021
COAD	-1.697
HGSC	2.192
ccRCC	-0.232
GBM	-0.048
HNSC	-0.516
LUAD	0.425
LUSC	0.147
non_ccRCC	0.49
PDAC	-0.74
UCEC

EIF2AK3-Ser660
Cancer	Intensity
BRCA	-1.439
COAD
HGSC
ccRCC	0.68
GBM	0.12
HNSC
LUAD	1.11
LUSC	-0.471
non_ccRCC
PDAC
UCEC

EIF2AK3-Ser705
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.707
GBM
HNSC	-0.707
LUAD
LUSC
non_ccRCC
PDAC
UCEC

EIF2AK3-Ser941
Cancer	Intensity
BRCA	0.741
COAD
HGSC
ccRCC	-1.96
GBM	0.242
HNSC	0.29
LUAD
LUSC	0.684
non_ccRCC
PDAC	0.004
UCEC

EIF2AK3-Ser943
Cancer	Intensity
BRCA	-1.617
COAD
HGSC	2.07
ccRCC	0.226
GBM	-0.082
HNSC	-0.331
LUAD	-0.373
LUSC	-0.018
non_ccRCC	0.69
PDAC	-0.564
UCEC

EIF2AK3-Ser945
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	0.953
HNSC
LUAD	-1.041
LUSC
non_ccRCC
PDAC	0.089
UCEC

EIF2AK3-Ser964
Cancer	Intensity
BRCA
COAD	-0.707
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

EIF2AK3-Thr406
Cancer	Intensity
BRCA
COAD	0.694
HGSC
ccRCC
GBM
HNSC	-1.146
LUAD
LUSC	0.452
non_ccRCC
PDAC
UCEC

EIF2AK4-Ser230
Cancer	Intensity
BRCA	-0.445
COAD
HGSC	2.732
ccRCC	-0.395
GBM	-0.115
HNSC	-0.278
LUAD	-0.804
LUSC	-0.508
non_ccRCC	0.268
PDAC	-0.152
UCEC	-0.303

EIF2AK4-Ser572
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC	0.78
LUAD
LUSC	-1.127
non_ccRCC
PDAC
UCEC	0.348

EIF2AK4-Ser770
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	-0.14
HNSC	-0.893
LUAD	-0.187
LUSC	-0.528
non_ccRCC	2.1
PDAC	-0.621
UCEC	0.269

EIF2AK4-Thr667
Cancer	Intensity
BRCA	-0.718
COAD	-0.434
HGSC	2.669
ccRCC	-0.092
GBM	0.155
HNSC	-0.464
LUAD	-0.237
LUSC	-0.857
non_ccRCC	0.254
PDAC	-0.857
UCEC	0.579

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
S	51	U	Triple-negative breast cancer	Phosphorylation	37834012
S	51	U	Lung adenocarcinoma	Phosphorylation	36226539

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