Tbio FOXO4 Forkhead box protein O4

Protein Summary

Description

Transcription factor involved in the regulation of the insulin signaling pathway. Binds to insulin-response elements (IREs) and can activate transcription of IGFBP1. Down-regulates expression of HIF1A and suppresses hypoxia-induced transcriptional activation of HIF1A-modulated genes. Also involved in negative regulation of the cell cycle. Involved in increased proteasome activity in embryonic stem cells (ESCs) by activating expression of PSMD11 in ESCs, leading to enhanced assembly of the 26S proteasome, followed by higher proteasome activity. This gene encodes a member of the O class of winged helix/forkhead transcription factor family. Proteins encoded by this class are regulated by factors involved in growth and differentiation indicating they play a role in these processes. A translocation involving this gene on chromosome X and the homolog of the Drosophila trithorax gene, encoding a DNA binding protein, located on chromosome 11 is associated with leukemia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

Uniprot Accession IDs

• P98177
• B7WPJ7
• O43821
• Q13720
• Q3KPF1
• Q8TDK9

Gene Name

• FOXO4

Ensembl ID

• ENST00000341558
• ENSP00000342209
• ENSG00000184481
• ENST00000374259
• ENSP00000363377

Symbol

• AFX
• AFX1
• MLLT7
• AFX
• AFX1
• MLLT7

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	0.9
hub protein	0.88
histone modification site profile	0.78
biological term	0.77
kinase	0.68

Related Tools

GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 164.43   (req: < 5)

Gene RIFs: 74   (req: <= 3)

Antibodies: 891   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 164.43   (req: >= 5)

Gene RIFs: 74   (req: > 3)

Antibodies: 891   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 30

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	forkhead box O4	VGNC:1385	473659
Macaque	forkhead box O4		698055
Mouse	forkhead box O4	MGI:1891915	54601
Rat	forkhead box O4	RGD:1561201	302415
Dog	forkhead box O4	VGNC:40964	100855644

Species	Name	OMA	EggNOG	Inparanoid
Chimp	forkhead box O4
Macaque	forkhead box O4
Mouse	forkhead box O4
Rat	forkhead box O4
Dog	forkhead box O4

Protein Structure (2 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-P98177-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 2 of 2

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (44)

Reactome (21)

KEGG (2)

PathwayCommons (14)

WikiPathways (7)

AKT phosphorylates targets in the nucleus (R-HSA-198693)

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Find Similar Targets

Items per page:

5

1 – 5 of 21

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	AKT phosphorylates targets in the nucleus	10 targets	R-HSA-198693
Reactome	Constitutive Signaling by AKT1 E17K in Cancer	26 targets	R-HSA-5674400
Reactome	Deubiquitination	278 targets	R-HSA-5688426
Reactome	Disease	1105 targets	R-HSA-1643685
Reactome	Diseases of signal transduction	387 targets	R-HSA-5663202

Name	Explore in Pharos	Explore in Source
AKT phosphorylates targets in the nucleus	10 targets	R-HSA-198693
Constitutive Signaling by AKT1 E17K in Cancer	26 targets	R-HSA-5674400
Deubiquitination	278 targets	R-HSA-5688426
Disease	1105 targets	R-HSA-1643685
Diseases of signal transduction	387 targets	R-HSA-5663202

Gene Ontology Terms (35)

Functions (10)

Components (5)

Processes (20)

Find Similar Targets

Items per page:

10

1 – 10 of 10

GO Term	Evidence	Assigned by
beta-catenin binding	Inferred from Direct Assay (IDA)	ParkinsonsUK-UCL
DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
DNA-binding transcription factor activity	Inferred from Direct Assay (IDA)	UniProtKB
sequence-specific DNA binding	Inferred from Direct Assay (IDA)	NTNU_SB
enzyme binding	Inferred from Physical Interaction (IPI)	UniProtKB
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
transcription factor binding	Inferred from Physical Interaction (IPI)	UniProtKB
DNA-binding transcription factor activity, RNA polymerase II-specific	Inferred from Sequence Alignment (ISA)	NTNU_SB
DNA-binding transcription activator activity, RNA polymerase II-specific	Inferred by Curator (IC)	NTNU_SB
promoter-specific chromatin binding	Inferred from Electronic Annotation (IEA)	Ensembl

Protein-Protein Interactions (111)

Explore Interacting Targets

1 – 10 of 111

• See Interactions on String-DB

AKT1

Tchem

Family: Kinase

Novelty: 0.00003185

Score: 0.99

Data Source: Reactome,STRINGDB

SIRT1

Tchem

Family: Epigenetic

Novelty: 0.00022265

Score: 0.985

Data Source: STRINGDB

CREBBP

Tchem

Family: Epigenetic

Novelty: 0.00111166

Score: 0.975

Data Source: Reactome,STRINGDB

USP7

Tchem

Family: Enzyme

Novelty: 0.00412878

Score: 0.968

Data Source: STRINGDB

MAPK8

Tchem

Family: Kinase

Novelty: 0.00055723

Score: 0.966

Data Source: STRINGDB

MDM2

Tchem

Family: Enzyme

Novelty: 0.00028385

Score: 0.963

Data Source: STRINGDB

EP300

Tchem

Family: Epigenetic

Novelty: 0.00055009

Score: 0.957

Data Source: Reactome,STRINGDB

PTEN

Tchem

Family: Enzyme

Novelty: 0.00013818

Score: 0.955

Data Source: STRINGDB

SMAD3

Tbio

Family: TF

Novelty: 0.00048058

Score: 0.954

Data Source: Reactome,STRINGDB

CTNNB1

Tchem

Novelty: 0.0000744

Score: 0.954

Data Source: STRINGDB

Publication Statistics

PubMed Score  164.43

PubMed score by year

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PubTator Score  83.09

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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3D-structure
Acetylation
Activator
Alternative splicing
Cell cycle
Chromosomal rearrangement
Complete proteome
Cytoplasm
Developmental protein
Differentiation

MGI Phenotype Find Similar Targets

hematopoietic system phenotype
immune system phenotype
reproductive system phenotype