PMADS

Id:	acc0732
Group:	2sens
Protein:	FOXO1
Gene Symbol:	FOXO1
Protein Id:	Q12778
Protein Name:	FOXO1_HUMAN
PTM:	phosphorylation
Site:	Thr24
Site Sequence:	EPLPRPRSCTWPLPRPEFSQS
Disease Category:	Cancer
Disease:	Lung Cancer
Disease Subtype:	NSCLC
Disease Cellline:	PC9
Disease Info:
Drug:	Ku0063794 + Erlotinib
Drug Info:	"Ku-0063794 is a cell-permeable, selective dual inhibitor of mTORC1 and mTORC2 with an IC50 of 10 nM, which induces G1-cell cycle arrest and autophagy, and inhibits tumor growth in renal cell carcinoma xenograft models. Erlotinib is a direct-acting EGFR tyrosine kinase inhibitor with an IC50 of 2 nM for human EGFR, used in the treatment of non-small cell lung cancer (NSCLC) by reducing EGFR autophosphorylation in intact tumor cells. "
Relation:	Ku0063794 + Erlotinib ➜ FOXO1-Thr24 DOWN ➜ Lung Cancer Alleviate
Effect:	modulate
Effect Info:	"In TKI-resistant cells, the mTOR–AKT–FOXO1 signaling pathway is dysregulated, with increased FOXO1 phosphorylation levels and decreased acetylation levels. The combined use of mTOR or PI3K inhibitors with erlotinib can overcome TKI resistance, inhibit cell proliferation, and induce apoptosis."
Note:	drug comb
Score:	4.0
Pubmed(PMID):	26036758
Sentence Index:	26036758_10-11
Sentence:	"Importantly, increasing FOXO1 acetylation by a HDAC inhibitor, depsipeptide, overcomes TKI resistance to effectively induce TKI-resistant NSCLC cell apoptosis. Together, FOXO1 plays dual roles in TKI resistance through posttranslational modifications in NSCLC and this study provides a possible strategy for treatment of TKI-resistant NSCLC patients."

Sequence & Structure:

MAEAPQVVEIDPDFEPLPRPRSCTWPLPRPEFSQSNSATSSPAPSGSAAANPDAAAGLPSASAAAVSADFMSNLSLLEESEDFPQAPGSVAAAVAAAAAAAATGGLCGDFQGPEAGCLHPAPPQPPPPGPLSQHPPVPPAAAGPLAGQPRKSSSSRRNAWGNLSYADLITKAIESSAEKRLTLSQIYEWMVKSVPYFKDKGDSNSSAGWKNSIRHNLSLHSKFIRVQNEGTGKSSWWMLNPEGGKSGKSPRRRAASMDNNSKFAKSRSRAAKKKASLQSGQEGAGDSPGSQFSKWPASPGSHSNDDFDNWSTFRPRTSSNASTISGRLSPIMTEQDDLGEGDVHSMVYPPSAAKMASTLPSLSEISNPENMENLLDNLNLLSSPTSLTVSTQSSPGTMMQQTPCYSFAPPNTSLNSPSPNYQKYTYGQSSMSPLPQMPIQTLQDNKSSYGGMSQYNCAPGLLKELLTSDSPPHNDIMTPVDPGVAQPNSRVLGQNVMMGPNSVMSTYGSQASHNKMMNPSSHTHPGHAQQTSAVNGRPLPHTVSTMPHTSGMNRLTQVKTPVQVPLPHPMQMSALGGYSSVSSCNGYGRMGLLHQEKLPSDLDGMFIERLDCDMESIIRNDLMDGDTLDFNFDNVLPNQSFPHSVKTTTHSWVSG

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!

FOXO1-Ser218
Cancer	Intensity
BRCA	1.611
COAD
HGSC
ccRCC
GBM	-0.033
HNSC
LUAD
LUSC	-0.786
non_ccRCC
PDAC	-0.882
UCEC	0.089

FOXO1-Ser256
Cancer	Intensity
BRCA	-0.041
COAD
HGSC	1.442
ccRCC
GBM	-0.737
HNSC	0.067
LUAD	-0.248
LUSC	-0.693
non_ccRCC	1.745
PDAC	-0.217
UCEC	-1.318

FOXO1-Ser276
Cancer	Intensity
BRCA	1.669
COAD
HGSC
ccRCC
GBM	0.177
HNSC	0.233
LUAD	0.118
LUSC	-0.216
non_ccRCC
PDAC	-0.248
UCEC	-1.734

FOXO1-Ser279
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.926
GBM
HNSC	-0.135
LUAD	1.061
LUSC
non_ccRCC
PDAC
UCEC

FOXO1-Ser287
Cancer	Intensity
BRCA	0.191
COAD	0.213
HGSC	-2.766
ccRCC	0.482
GBM	0.205
HNSC	0.041
LUAD	0.127
LUSC	0.229
non_ccRCC	1.379
PDAC	0.042
UCEC	-0.142

FOXO1-Ser290
Cancer	Intensity
BRCA
COAD	0.707
HGSC
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	-0.707

FOXO1-Ser298
Cancer	Intensity
BRCA	0.714
COAD	-0.074
HGSC
ccRCC	-0.663
GBM	-0.928
HNSC	-0.11
LUAD	0.011
LUSC	0.835
non_ccRCC	1.974
PDAC	-0.162
UCEC	-1.597

FOXO1-Ser301
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	0.966
HNSC	-1.031
LUAD	0.065
LUSC
non_ccRCC
PDAC
UCEC

FOXO1-Ser303
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	-0.653
HNSC	1.461
LUAD
LUSC
non_ccRCC
PDAC	-0.642
UCEC	-0.166

FOXO1-Ser319
Cancer	Intensity
BRCA
COAD	0.846
HGSC	-1.441
ccRCC
GBM	0.423
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	0.172

FOXO1-Ser322
Cancer	Intensity
BRCA
COAD	0.707
HGSC	-0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

FOXO1-Ser329
Cancer	Intensity
BRCA
COAD	0.095
HGSC	-0.665
ccRCC
GBM	1.377
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	-0.808

FOXO1-Ser470
Cancer	Intensity
BRCA
COAD	-0.366
HGSC	1.256
ccRCC
GBM
HNSC	0.224
LUAD
LUSC
non_ccRCC
PDAC
UCEC	-1.113

FOXO1-Thr478
Cancer	Intensity
BRCA
COAD
HGSC	-0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	0.707

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
T	24	D	Head and neck squamous cell carcinoma	Phosphorylation	21281788
T	24	U	Breast cancer	Phosphorylation	36797347
T	24	U	Prostate cancer	Phosphorylation	36720852

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