| + |
AKT | down-regulates activity 
phosphorylation
|
FOXO4 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251477 |
Ser197 |
APRRRAAsMDSSSKL |
Mus musculus |
NIH-3T3-A14 Cell |
| pmid |
sentence |
| 10217147 |
Here we show that protein kinase B phosphorylates AFX, a human orthologue of daf -16 (refs 5, 6, 9), both in vitro and in vivo. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251478 |
Ser262 |
TFRPRSSsNASSVST |
Mus musculus |
|
| pmid |
sentence |
| 10217147 |
Here we show that protein kinase B phosphorylates AFX, a human orthologue of daf -16 (refs 5, 6, 9), both in vitro and in vivo. |
|
| Publications: |
2 |
Organism: |
Mus Musculus |
| Pathways: | Insulin Signaling |
| + |
AKT | down-regulates
phosphorylation
|
FOXO4 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-141416 |
Ser197 |
APRRRAAsMDSSSKL |
Homo sapiens |
|
| pmid |
sentence |
| 16272144 |
Foxo4 transcription factor, also referred to afx, contains three putative phosphorylation motif sites for protein kinase b (pkb), thr32, ser197, and ser262, and it is proposed that phosphorylated foxo4 stays in the cytosol and is imported to the nucleus through dephosphorylation to induce target gene expression |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-141420 |
Ser262 |
TFRPRSSsNASSVST |
Homo sapiens |
|
| pmid |
sentence |
| 16272144 |
Foxo4 transcription factor, also referred to afx, contains three putative phosphorylation motif sites for protein kinase b (pkb), thr32, ser197, and ser262, and it is proposed that phosphorylated foxo4 stays in the cytosol and is imported to the nucleus through dephosphorylation to induce target gene expression |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-141424 |
Thr32 |
QSRPRSCtWPLPRPE |
Homo sapiens |
|
| pmid |
sentence |
| 16272144 |
Foxo4 transcription factor, also referred to afx, contains three putative phosphorylation motif sites for protein kinase b (pkb), thr32, ser197, and ser262, and it is proposed that phosphorylated foxo4 stays in the cytosol and is imported to the nucleus through dephosphorylation to induce target gene expression |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-174021 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21620960 |
Akt phosphorylates members of the foxo factors (forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localisation. In particular, akt phosphorylates foxo1 on thr24, ser256 and ser319. Foxo 3alfa and foxo4 are phosphorylated on equivalent sites. In addition, phosphorylation of afx by protein kinase b inhibits its transcriptional activity. |
|
| Publications: |
4 |
Organism: |
Homo Sapiens |
| Pathways: | Insulin Signaling |
| + |
AKT1 | down-regulates activity
phosphorylation
|
FOXO4 |
0.763 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252568 |
Ser197 |
APRRRAAsMDSSSKL |
Mus musculus |
NIH-3T3-A14 Cell |
| pmid |
sentence |
| 10217147 |
Here we show that protein kinase B phosphorylates AFX, a human orthologue of daf -16 (refs 5, 6, 9), both in vitro and in vivo. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252569 |
Ser262 |
TFRPRSSsNASSVST |
Mus musculus |
NIH-3T3-A14 Cell |
| pmid |
sentence |
| 10217147 |
Here we show that protein kinase B phosphorylates AFX, a human orthologue of daf -16 (refs 5, 6, 9), both in vitro and in vivo. |
|
| Publications: |
2 |
Organism: |
Mus Musculus |
| + |
AKT1 | down-regulates
phosphorylation
|
FOXO4 |
0.763 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252484 |
Ser197 |
APRRRAAsMDSSSKL |
Homo sapiens |
|
| pmid |
sentence |
| 16272144 |
Foxo4 transcription factor, also referred to afx, contains three putative phosphorylation motif sites for protein kinase b (pkb), thr32, ser197, and ser262, and it is proposed that phosphorylated foxo4 stays in the cytosol and is imported to the nucleus through dephosphorylation to induce target gene expression |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252485 |
Ser262 |
TFRPRSSsNASSVST |
Homo sapiens |
|
| pmid |
sentence |
| 16272144 |
Foxo4 transcription factor, also referred to afx, contains three putative phosphorylation motif sites for protein kinase b (pkb), thr32, ser197, and ser262, and it is proposed that phosphorylated foxo4 stays in the cytosol and is imported to the nucleus through dephosphorylation to induce target gene expression |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252486 |
Thr32 |
QSRPRSCtWPLPRPE |
Homo sapiens |
|
| pmid |
sentence |
| 16272144 |
Foxo4 transcription factor, also referred to afx, contains three putative phosphorylation motif sites for protein kinase b (pkb), thr32, ser197, and ser262, and it is proposed that phosphorylated foxo4 stays in the cytosol and is imported to the nucleus through dephosphorylation to induce target gene expression |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252515 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21620960 |
Akt phosphorylates members of the foxo factors (forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localisation. In particular, akt phosphorylates foxo1 on thr24, ser256 and ser319. Foxo 3alfa and foxo4 are phosphorylated on equivalent sites. In addition, phosphorylation of afx by protein kinase b inhibits its transcriptional activity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-175291 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21798082 |
Akt inactivates protein degradation by phosphorylating and thus repressing the transcription factors of the foxo family, and stimulates protein synthesis via the mammalian target of rapamycin (mtor) and glycogen synthase kinase 3b (gsk3b). |
|
| Publications: |
5 |
Organism: |
Homo Sapiens |
| + |
JNK | up-regulates 
phosphorylation
|
FOXO4 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-168754 |
Ser230 |
PEGATPTsPVGHFAK |
Homo sapiens |
Melanoma Cell |
| pmid |
sentence |
| 20959475 |
Braf(v600e) signaling through mitogen-activated protein kinase/extracellular signal-regulated kinase kinase resulted in increased reactive oxygen species levels and c-jun nh(2) terminal kinase-mediated activation of foxo4 via its phosphorylation on thr(223), ser(226), thr(447), and thr(451). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-168758 |
Thr227 |
PAPPEGAtPTSPVGH |
Homo sapiens |
Melanoma Cell |
| pmid |
sentence |
| 20959475 |
Braf(v600e) signaling through mitogen-activated protein kinase/extracellular signal-regulated kinase kinase resulted in increased reactive oxygen species levels and c-jun nh(2) terminal kinase-mediated activation of foxo4 via its phosphorylation on thr(223), ser(226), thr(447), and thr(451). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-168762 |
Thr451 |
PIPKALGtPVLTPPT |
Homo sapiens |
Melanoma Cell |
| pmid |
sentence |
| 20959475 |
Braf(v600e) signaling through mitogen-activated protein kinase/extracellular signal-regulated kinase kinase resulted in increased reactive oxygen species levels and c-jun nh(2) terminal kinase-mediated activation of foxo4 via its phosphorylation on thr(223), ser(226), thr(447), and thr(451). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-168766 |
Thr455 |
ALGTPVLtPPTEAAS |
Homo sapiens |
Melanoma Cell |
| pmid |
sentence |
| 20959475 |
Braf(v600e) signaling through mitogen-activated protein kinase/extracellular signal-regulated kinase kinase resulted in increased reactive oxygen species levels and c-jun nh(2) terminal kinase-mediated activation of foxo4 via its phosphorylation on thr(223), ser(226), thr(447), and thr(451). |
|
| Publications: |
4 |
Organism: |
Homo Sapiens |
| Tissue: |
Skin |
| + |
CSNK1A1 | down-regulates quantity by destabilization
phosphorylation
|
FOXO4 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277325 |
Ser265 |
PRSSSNAsSVSTRLS |
Homo sapiens |
HCT-116 Cell |
| pmid |
sentence |
| 28945225 |
Here we report that CK1α similarly destabilizes FOXO4 in RAS-mutant cells by phosphorylation at serines 265/268. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277326 |
Ser268 |
SSNASSVsTRLSPLR |
Homo sapiens |
HCT-116 Cell |
| pmid |
sentence |
| 28945225 |
Here we report that CK1α similarly destabilizes FOXO4 in RAS-mutant cells by phosphorylation at serines 265/268. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
AKT2 | down-regulates activity
phosphorylation
|
FOXO4 |
0.604 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251491 |
Thr32 |
QSRPRSCtWPLPRPE |
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 11313479 |
Phosphorylation of AFX by PKB occurs in the nucleus. Phosphorylation of S193 reduces the rate of nuclear import. PKB-mediated phosphorylation of AFX, therefore, attenuates the import of the transcription factor, which shifts the localization of the protein from the nucleus to the cytoplasm and results in the inhibition of AFX transcriptional activity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248055 |
Thr32 |
QSRPRSCtWPLPRPE |
Homo sapiens |
|
| pmid |
sentence |
| 16272144 |
FOXO4 transcription factor, also referred to AFX, contains three putative phosphorylation motif sites for protein kinase B (PKB), Thr32, Ser197, and Ser262, and it is proposed that phosphorylated FOXO4 stays in the cytosol and is imported to the nucleus through dephosphorylation to induce target gene expression.[...]These results indicate that phosphorylation at Thr32 and Ser197 is indispensable, whereas that at Ser262 is not critical, for regulation of the nuclear localization and transcriptional activity of FOXO4 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-233529 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21620960 |
Akt phosphorylates members of the foxo factors (forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localisation. In particular, akt phosphorylates foxo1 on thr24, ser256 and ser319. Foxo 3alfa and foxo4 are phosphorylated on equivalent sites. In addition, phosphorylation of afx by protein kinase b inhibits its transcriptional activity. |
|
| Publications: |
3 |
Organism: |
Mus Musculus, Homo Sapiens |
| + |
RALA | up-regulates activity
phosphorylation
|
FOXO4 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248003 |
Thr451 |
PIPKALGtPVLTPPT |
Mus musculus |
|
| pmid |
sentence |
| 11689711 |
We conclude that Ral-mediated phosphorylation of threonines 447 and 451 is required for proper activity of AFX-WT. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249665 |
Thr455 |
ALGTPVLtPPTEAAS |
Mus musculus |
|
| pmid |
sentence |
| 11689711 |
We conclude that Ral-mediated phosphorylation of threonines 447 and 451 is required for proper activity of AFX-WT. |
|
| Publications: |
2 |
Organism: |
Mus Musculus |
| + |
MAPK8 | up-regulates
phosphorylation
|
FOXO4 |
0.611 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-130381 |
Thr451 |
PIPKALGtPVLTPPT |
Homo sapiens |
|
| pmid |
sentence |
| 15538382 |
Upon treatment of cells with h2o2, the small gtpase ral is activated and this results in a jnk-dependent phosphorylation of foxo4 on threonine 447 and threonine 451. This ral-mediated, jnk-dependent phosphorylation is involved in the nuclear translocation and transcriptional activation of foxo4 after h2o2 treatment. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-130385 |
Thr455 |
ALGTPVLtPPTEAAS |
Homo sapiens |
|
| pmid |
sentence |
| 15538382 |
Upon treatment of cells with h2o2, the small gtpase ral is activated and this results in a jnk-dependent phosphorylation of foxo4 on threonine 447 and threonine 451. This ral-mediated, jnk-dependent phosphorylation is involved in the nuclear translocation and transcriptional activation of foxo4 after h2o2 treatment. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
FOXO4 | up-regulates quantity by expression 
transcriptional regulation
|
TRIM63 |
0.341 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236557 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21798082 |
Foxo factors are required for the transcriptional regulation of the ubiquitin ligases atrogin-1, also called muscle atrophy f-box (mafbx) and muscle ring finger 1 (murf1), leading to the ubiquitylation of myosin and other muscle proteins, and their degradation via the proteasome. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Muscle |
| + |
TSC22D3 | down-regulates activity
relocalization
|
FOXO4 |
0.253 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256148 |
|
|
Homo sapiens |
HL-60 Cell |
| pmid |
sentence |
| 20018851 |
GILZ inhibits FOXO1, FOXO3, and FOXO4 transcriptional activities measured with natural or synthetic FOXO-responsive promoters in HL-60 cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKAA1 | up-regulates
phosphorylation
|
FOXO4 |
0.367 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-157947 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17900900 |
The energy sensor amp-activated protein kinase (ampk) has been shown to directly phosphorylate foxo factors at six regulatory sites that are distinct from the akt phosphorylation sites, resulting in foxo activation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SIRT1 | up-regulates
deacetylation
|
FOXO4 |
0.744 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-124714 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15126506 |
Deacetylation of foxos involves binding of the nad-dependent deacetylase hsir2(sirt1). Accordingly, hsir2(sirt1)-mediated deacetylation precludes foxo inhibition through acetylation and thereby prolongs foxo-dependent transcription of stress-regulating genes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CDK2 | down-regulates
phosphorylation
|
FOXO4 |
0.516 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-183655 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19188143 |
Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AMPK | up-regulates
phosphorylation
|
FOXO4 |
0.349 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-216484 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17900900 |
The energy sensor amp-activated protein kinase (ampk) has been shown to directly phosphorylate foxo factors at six regulatory sites that are distinct from the akt phosphorylation sites, resulting in foxo activation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DYRK1A | down-regulates
phosphorylation
|
FOXO4 |
0.317 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-183677 |
|
|
Homo sapiens |
Breast Cancer Cell, Prostate Gland Cancer Cell, Leukemia Cell, Glioblastoma Cell |
| pmid |
sentence |
| 19188143 |
Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FOXO4 | up-regulates quantity by expression
transcriptional regulation
|
IDH1 |
0.265 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260091 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25648147 |
We identify FOXOs as transcriptional activators of IDH1. FOXOs promote IDH1 expression and thereby maintain the cytosolic levels of α-ketoglutarate and NADPH. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260102 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25648147 |
We identify FOXOs as transcriptional activators of IDH1. FOXOs promote IDH1 expression and thereby maintain the cytosolic levels of α-ketoglutarate and NADPH. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
CREB1 | down-regulates activity
binding
|
FOXO4 |
0.309 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-124711 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15126506 |
We provide evidence that the acetyltransferase creb-binding protein (cbp) binds foxo resulting in acetylation of foxo. This acetylation inhibits foxo transcriptional activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FOXO4 | up-regulates quantity by expression
transcriptional regulation
|
FBXO32 |
0.377 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236554 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21798082 |
Foxo factors are required for the transcriptional regulation of the ubiquitin ligases atrogin-1, also called muscle atrophy f-box (mafbx) and muscle ring finger 1 (murf1), leading to the ubiquitylation of myosin and other muscle proteins, and their degradation via the proteasome. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Muscle |
| + |
CSNK1A1 | down-regulates
phosphorylation
|
FOXO4 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-183664 |
|
|
Homo sapiens |
Breast Cancer Cell, Prostate Gland Cancer Cell, Leukemia Cell, Glioblastoma Cell |
| pmid |
sentence |
| 19188143 |
Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FOXS1 | down-regulates quantity by repression
transcriptional regulation
|
FOXO4 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261611 |
|
|
Bos taurus |
Aortic Smooth Muscle Cell |
| pmid |
sentence |
| 18288644 |
Fkhl18 suppressed the transcriptional activity of FoxO3a and FoxO4. |
|
| Publications: |
1 |
Organism: |
Bos Taurus |
| + |
MDM2 | down-regulates activity
ubiquitination
|
FOXO4 |
0.628 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278656 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18665269 |
Mdm2 Induces Mono-Ubiquitination of FOXO4.|higher amounts of Mdm2 transfected resulted in reduced FOXO4 transcriptional activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
STK4 | up-regulates
phosphorylation
|
FOXO4 |
0.424 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178193 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18394876 |
The other major signaling modules that directly regulate the activity of the foxo factors include the stress-activated jun-n-terminal kinase (jnk), the mammalian ortholog of the ste20-like protein kinase (mst1), and the deacetylase sirt1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
FOXO4
- 
- 