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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

FOXO3 Gene

protein-coding GIFtS: 61
GCID: GC06P108881

forkhead box O3

(Previous symbols: FKHRL1, FOXO3A)

Explore 64 diseases affiliated with
FOXO3 via

MalaCards

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Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Forkhead Box O3¹ ²		FKHRL1P2²
FKHRL1¹ ² ³ ⁵		Forkhead Box O3A²
FOXO3A¹ ² ³ ⁵		Forkhead Box Protein O3²
AF6q21¹ ²		Forkhead Homolog (Rhabdomyosarcoma) Like 1²
FOXO2¹ ²		Forkhead, Drosophila, Homolog Of, In Rhabdomyosarcoma-Like 1²
Forkhead In Rhabdomyosarcoma-Like 1² ³		AF6q21 Protein³

External Ids:	HGNC: 3821¹	Entrez Gene: 2309²	Ensembl: ENSG00000118689⁷	OMIM: 602681⁵	UniProtKB: O43524³

Export aliases for FOXO3 gene to outside databases

Previous GC identifers: GC06P108988 GC06P106448

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for FOXO3:

This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead

domain. This gene likely functions as a trigger for apoptosis through expression of genes necessary for cell death.

Translocation of this gene with the MLL gene is associated with secondary acute leukemia. Alternatively spliced

transcript variants encoding the same protein have been observed. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: FOXO3_HUMAN, O43524

Function: Transcriptional activator which triggers apoptosis in the absence of survival factors, including neuronal

cell death upon oxidative stress. Recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3'. Participates in

post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and

miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its

translation

Gene Wiki entry for FOXO3

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000006.11 NC_018917.1 NT_025741.15

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the FOXO3 gene promoter:
AP-1 STAT5A
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 5): FOXO3 promoter sequence

Search SABiosciences Chromatin IP Primers for FOXO3

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat FOXO3

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 6q21 Ensembl cytogenetic band: 6q21 HGNC cytogenetic band: 6q21

FOXO3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
FOXO3 gene location

GeneLoc information about chromosome 6 GeneLoc Exon Structure

GeneLoc location for GC06P108881: view genomic region (about GC identifiers)

Start:	108,881,026 bp from pter	End:	109,005,977 bp from pter
Size:	124,952 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: FOXO3_HUMAN, O43524 (See protein sequence)

Recommended Name: Forkhead box protein O3

Size: 673 amino acids; 71277 Da

Subunit: Interacts with YWHAB/14-3-3-beta and YWHAZ/14-3-3-zeta, which are required for cytosolic sequestration. Upon

oxidative stress, interacts with STK4/MST1, which disrupts interaction with YWHAB/14-3-3-beta and leads to nuclear

translocation. Interacts with PIM1. Interacts with DDIT3/CHOP

Subcellular location: Cytoplasm, cytosol. Nucleus. Note=Translocates to the nucleus upon oxidative stress and in the

absence of survival factors

4 PDB 3D structures from and Proteopedia for FOXO3:

2K86 (3D)

2LQH (3D)

2LQI (3D)

2UZK (3D)

Secondary accessions: E1P5E6 O15171 Q5T2I7 Q9BZ04

Explore the universe of human proteins at neXtProt for FOXO3: NX_O43524

Post-translational modifications:

In the presence of survival factors such as IGF-1, phosphorylated on Thr-32 and Ser-253 by AKT1/PKB. This

phosphorylated form then interacts with 14-3-3 proteins and is retained in the cytoplasm. Survival factor withdrawal

induces dephosphorylation and promotes translocation to the nucleus where the dephosphorylated protein induces

transcription of target genes and triggers apoptosis. Although AKT1/PKB doesn't appear to phosphorylate Ser-315

directly, it may activate other kinases that trigger phosphorylation at this residue. Phosphorylated by STK4/MST1 on

Ser-209 upon oxidative stress, which leads to dissociation from YWHAB/14-3-3-beta and nuclear translocation.

Phosphorylated by PIM1. Phosphorylation by AMPK leads to the activation of transcriptional activity without affecting

subcellular localization. Phosphorylation by MAPKAPK5 promotes nuclear localization and DNA-binding, leading to

induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC

transcript and prevent its translation¹

Heavyly methylated by SET9 which decreases stability, while moderately increasing transcriptional activity. The main

methylation site is Lys-271. Methylation doesn't affect subcellular location¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_O43524

FOXO3 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_001446.1 NP_963853.1

ENSEMBL proteins:

ENSP00000339527 ENSP00000385824 ENSP00000446316

Reactome Protein details: O43524
Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	OriGene Purified Proteins (see all 2): FOXO3 OriGene Protein Over-expression Lysate (see all 3): FOXO3 OriGene Custom Protein Services for FOXO3
	GenScript Custom Purified and Recombinant Proteins Services for FOXO3
	Novus Biologicals FOXO3 Proteins Novus Biologicals FOXO3 Lysates
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for FOXO3

Gene Ontology (GO): 5/7 cellular component terms (GO ID links to tree view) (see all 7): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005624	membrane fraction	--	--
GO:0005634	nucleus	IDA	--
GO:0005654	nucleoplasm	TAS	--
GO:0005667	transcription factor complex	IBA	--
GO:0005737	cytoplasm	IDA	--

FOXO3 for ontologies About GeneDecksing

FOXO3 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of FOXO3
	R&D Systems Antibodies for FOXO3
	Cell Signaling Technology (CST) Antibodies for FOXO3 (FOXO3A)
	OriGene Antibodies (see all 5): FOXO3 OriGene Custom Antibody Services for FOXO3
	GenScript Custom Superior Antibodies Services for FOXO3
	Novus Biologicals FOXO3 Antibodies
	Abcam antibodies for FOXO3
	Uscn Antibodies for FOXO3
	ThermoFisher Antibody for FOXO3

Assay Products for FOXO3:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for FOXO3
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for FOXO3

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

FOXO3 for domains About GeneDecksing

3 InterPro domains/families:

IPR011991 WHTH_trsnscrt_rep_DNA-bd_dom

IPR018122 TF_fork_head_CS

IPR001766 TF_fork_head

Graphical View of Domain Structure for InterPro Entry O43524

ProtoNet protein and cluster: O43524

UniProtKB/Swiss-Prot: FOXO3_HUMAN, O43524

Similarity: Contains 1 fork-head DNA-binding domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: FOXO3_HUMAN, O43524

Function: Transcriptional activator which triggers apoptosis in the absence of survival factors, including neuronal

cell death upon oxidative stress. Recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3'. Participates in

post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and

miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its

translation

		10/364 SABiosciences Target genes for FOXO3 (see all 364):
		ABCD4 ABRA ACAD10 ACOXL ACTG2 ADAMTS15 AFAP1L1 AFM AGBL4 AKAP14

miRNA Products:		miRTarBase miRNAs that target FOXO3: hsa-mir-221 (MIRT000434), hsa-mir-182 (MIRT000671), hsa-mir-197 (MIRT004198), hsa-mir-222 (MIRT000433), hsa-mir-155 (MIRT004495), hsa-mir-96 (MIRT005450)

		OriGene 3'-UTR Clone (see all 2): FOXO3 Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat FOXO3
		8/134 QIAGEN miScript miRNA Assays for microRNAs that regulate FOXO3 (see all 134):
		hsa-miR-579 hsa-miR-520f hsa-miR-1245 hsa-miR-3074-3p hsa-miR-138-2* hsa-miR-3916 hsa-miR-520b hsa-miR-186*

		Browse SwitchGear 3'UTR luciferase reporter plasmids

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for FOXO3 (see all 10) OriGene shRNA RFP: FOXO3 OriGene siRNA: FOXO3
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat FOXO3

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for FOXO3

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for FOXO3 (see all 4) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for FOXO3 (see all 3) OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 2): FOXO3 (NM_001455)
		Browse Sino Biological Human cDNA Clones
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for FOXO3
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat FOXO3

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for FOXO3
		Search LifeMap BioReagents cell lines for FOXO3

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for FOXO3

Gene Ontology (GO): 5/9 molecular function terms (GO ID links to tree view) (see all 9): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003677	DNA binding	IDA	--
GO:0003690	double-stranded DNA binding	IBA	--
GO:0003700	sequence-specific DNA binding transcription factor activity	IDA	14734530
GO:0003705	RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity	IBA	--
GO:0005515	protein binding	IPI	--

FOXO3 for ontologies           About GeneDecksing

Animal Models:
     Mouse knock-outs for FOXO3: Foxo3^tm1.1Rdp Foxo3^tm1Nmt
     13 MGI mutant phenotypes (inferred from 6 alleles) (MGI details for Foxo3):

cardiovascular system	cellular	digestive/alimentary	endocrine/exocrine gland	hematopoietic system
homeostasis/metabolism	immune system	integument	mortality/aging	renal/urinary system
reproductive system	respiratory system	tumorigenesis

FOXO3 for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/45 super-pathways (see all 45) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Signaling by FGFR

8/12 pathways (see all 12)
Signaling by FGFR	1.00	DAP12 signaling	0.83
Downstream signaling of activated FGFR	0.92	Signaling by EGFR in Cancer	0.83
Signaling by FGFR in disease	0.91	DAP12 interactions	0.76
Signaling by ERBB2	0.89	Signaling by PDGF	0.72

PIP3 activates AKT signaling

8/10 pathways (see all 10)
PIP3 activates AKT signaling	1.00	PI3K/AKT activation	0.97
PI3K/AKT Signaling in Cancer	1.00	GAB1 signalosome	0.96
PI3K events in ERBB2 signaling	1.00	Constitutive PI3K/AKT Signaling in Cancer	0.88
PI3K events in ERBB4 signaling	1.00	Signaling by SCF-KIT	0.72

IL-9 Signaling Pathways

IL-9 Signaling Pathways	1.00	IL-2 Signaling Pathways	0.88
IL-21 Signaling Pathways	0.90	IL-15 Signaling Pathways	0.86
IL-7 Signaling Pathways	0.90	IL-4 Signaling Pathways	0.80
Common Cytokine Receptor Gamma-Chain Family Signaling Pathways	0.90	IL-7 Signaling Pathway	0.38

Development IGF-RI signaling

	Development IGF-RI signaling	1.00			Signal transduction_AKT signaling	0.49
	Development_IGF-1 receptor signaling	0.99			Signal transduction AKT signaling	0.49

Endometrial cancer

	Endometrial cancer	1.00			Signal transduction PTEN pathway	0.45
	Signal transduction_PTEN pathway	0.45

Pathway sources
See GeneCards unified pathways
Show all pathways

4 EMD Millipore Pathways for FOXO3

	Signal transduction PTEN pathway
	Signal transduction AKT signaling
	Translation Non-genomic (rapid) action of Androgen Receptor
	Development IGF-RI signaling

5/8 R&D Systems Pathways for FOXO3 (see all 8)

	IL-21 Signaling Pathways
	IL-2 Signaling Pathways
	IL-4 Signaling Pathways
	IL-7 Signaling Pathways
	TGF-beta Signaling Pathways

5/9 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for FOXO3 (see all 9)

	ErbB2-ErbB3 Heterodimers
	14-3-3 Induced Apoptosis
	IGF1R Signaling
	PI3K Signaling in B-Lymphocyte
	ERK5 Signaling

2 Cell Signaling Technology (CST) Pathways for FOXO3

	MAP Kinase Signaling
	PI3K / Akt Signaling

4 GeneGo (Thomson Reuters) Pathways for FOXO3

	Signal transduction AKT signaling
	Signal transduction PTEN pathway
	Development IGF-1 receptor signaling
	Translation Non-genomic (rapid) action of Androgen Receptor

5/19 BioSystems Pathways for FOXO3 (see all 19)

	Signaling Pathways in Glioblastoma
	DNA damage response (only ATM dependent)
	TGF-beta Receptor Signaling Pathway
	Energy Metabolism
	IL-7 Signaling Pathway

5/32 Reactome Pathways for FOXO3 (see all 32)

	AKT phosphorylates targets in the nucleus
	Developmental Biology
	Signaling by EGFR in Cancer
	Disease
	Signaling by ERBB2

4 Kegg Pathways (Kegg details for FOXO3):

	Chemokine signaling pathway
	Neurotrophin signaling pathway
	Endometrial cancer
	Non-small cell lung cancer

FOXO3 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for FOXO3

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/323 Interacting proteins for FOXO3 (O43524^{1, 2, 3} ENSP00000339527⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 323)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
PPP2R1A	P30153²^,³, ENSP00000324804⁴	MINT-8288927 MINT-8288942 I2D: score=2 STRING: ENSP00000324804
SIRT1	Q96EB6¹^,³, ENSP00000212015⁴	EBI-1644164,EBI-1802965 I2D: score=3 STRING: ENSP00000212015
MAPK6	Q16659²^,³	MINT-8261131 I2D: score=2
YWHAZ	P63104²^,³, ENSP00000309503⁴	MINT-14323 MINT-8005353 MINT-8005360 I2D: score=5 STRING: ENSP00000309503
RPL9	P32969³	I2D: score=1

About this table

Gene Ontology (GO): 5/26 biological process terms (GO ID links to tree view) (see all 26): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	IMP	18787191
GO:0001542	ovulation from ovarian follicle	IBA	--
GO:0001544	initiation of primordial ovarian follicle growth	IBA	--
GO:0001547	antral ovarian follicle growth	IBA	--
GO:0001556	oocyte maturation	IBA	--

FOXO3 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

FOXO3 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for FOXO3
10/20 Novoseek chemical compound relationships for FOXO3 gene (see all 20) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
phosphatidylinositol	70.8	11	19911116 (1), 14701673 (1), 15207915 (1), 16687394 (1) (see all 9)
ly294002	67.6	10	11694570 (1), 19911116 (1), 10944433 (1), 14656735 (1) (see all 9)
phosphoinositide	52.3	8	19302476 (1), 12150827 (1), 12504093 (1), 20484037 (1) (see all 6)
imatinib	48.7	17	17900262 (5), 15509806 (3), 17132628 (2), 15277706 (1) (see all 6)
wortmannin	43.3	1	18385518 (1)
glycogen	36.4	6	18476967 (1), 11237865 (1), 17522055 (1), 12139625 (1) (see all 5)
tyrosine	29.7	6	17900262 (2), 19285077 (1), 12456669 (1), 12506011 (1)
rapamycin	24.5	2	18476967 (1), 12782577 (1)
threonine	15.2	1	12359217 (1)
l-nmma	8.07	5	17044646 (3)

Search CenterWatch for drugs/clinical trials and news about FOXO3

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for FOXO3 gene (2 alternative transcripts):

NM_001455.3 NM_201559.2

Unigene Cluster for FOXO3:

Forkhead box O3

Hs.220950 [show with all ESTs]

Unigene Representative Sequence: NM_001455

3 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000343882(uc003psk.2 uc011ean.1 uc010kdj.1) ENST00000406360(uc003psm.2)

ENST00000540898

miRNA Products:		OriGene 3'-UTR Clone (see all 2): FOXO3 Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat FOXO3
		8/134 QIAGEN miScript miRNA Assays for microRNAs that regulate FOXO3 (see all 134):
		hsa-miR-579 hsa-miR-520f hsa-miR-1245 hsa-miR-3074-3p hsa-miR-138-2* hsa-miR-3916 hsa-miR-520b hsa-miR-186*

		Browse SwitchGear 3'UTR luciferase reporter plasmids

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		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat FOXO3

Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for FOXO3 (see all 4) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for FOXO3 (see all 3) OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 2): FOXO3 (NM_001455)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for FOXO3
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		SABiosciences RT² qPCR Primer Assay in human, mouse, rat FOXO3
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat FOXO3
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat FOXO3

Additional cDNA sequence:

AB072905.1 AF032886.1 AJ001589.1 AK024103.1 AK092357.1 AK122861.1 AK301304.1 AK303933.1

AK311587.1 BC020227.1 BC021224.2 BC045800.1 BC068552.1 CR749261.1

19 DOTS entries:

DT.100649722 DT.95294944 DT.100755530 DT.216108 DT.121004366 DT.100649556 DT.101981892 DT.97771444

DT.100823907 DT.100755532 DT.100726911 DT.95200828 DT.95354316 DT.121313784 DT.91901643 DT.95162771

DT.100702119 DT.91746714 DT.99940058

24/142 AceView cDNA sequences (see all 142):

AI521727 AI075785 AI358905 AI554317 BE502772 BC021224 AA603521 N29118

BM718517 BX106027 AI919238 BQ214507 BC068552 AA453067 BG057950 NM_201559

BF222626 AI421125 NM_001455 CA389775 CA306641 AA465236 AA602472 AA465591

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

FOXO3 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: TAAATAAAGC

About this image

FOXO3 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

3 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Ovary

Primary Follicle

Primary Oocyte

Female Gametocytes, Germ Cells

Ovary

Primordial Follicle

Primary Oocyte

Female Gametocytes, Germ Cells

Head Mesenchyme

Branchial Arch 1

Paraxial Mesoderm Cells

Bone, Skeletal Muscle

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See FOXO3 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for FOXO3

SOURCE GeneReport for Unigene cluster: Hs.220950

UniProtKB/Swiss-Prot: FOXO3_HUMAN, O43524

Tissue specificity: Ubiquitous

SABiosciences Expression via Pathway-Focused PCR Arrays including FOXO3 (see all 6):

Leukemia in human mouse rat

p53 Signaling Pathway in human mouse rat

PI3K-AKT Signaling Pathway in human mouse rat

EGF / PDGF Signaling Pathway in human mouse rat

Skeletal Muscle: Myogenesis & Myopathy in human mouse rat

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for FOXO3 gene from 6/22 species (see all 22) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	FOXO3¹	forkhead box O3	80.11(n) 88.74(a)		421769 XM_001234495.2 XP_001234496.2
lizard (Anolis carolinensis)	Reptilia	FOXO3⁶	--	87(a)	1 ↔ 1	1(190741042-190742406)
African clawed frog (Xenopus laevis)	Amphibia	Xl.2074²	Xenopus laevis transcribed sequences	84.27(n)		BJ070632.1
zebrafish (Danio rerio)	Actinopterygii	AF114262.1²	--	77.12(n)		30296 AF114262.1
fruit fly (Drosophila melanogaster)	Insecta	foxo¹	forkhead box, sub-group O	51.3(n) 46.79(a)		41709 NM_206483.2 NP_996205.1
worm (Caenorhabditis elegans)	Secernentea	daf-16⁶	Forkhead box protein O	28(a)	1 → many	I(10750332-10776689)

ENSEMBL Gene Tree for FOXO3 (if available)
TreeFam Gene Tree for FOXO3 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for FOXO3 gene

FOXO4² FOXO6² FOXO1²

5 SIMAP similar genes for FOXO3 using alignment to 2 protein entries: FOXO3_HUMAN (see all proteins):

DKFZp781A0677 FKHRL1P2 FOXO1 FOXO4 FOXO6

FOXO3 for paralogs About GeneDecksing

1 Pseudogenes.org Pseudogene for FOXO3
PGOHUM00000236954

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
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SNP ID	Valid	Clinical significance	Chr 6 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs11969027^1,2	C,A,H	--	108879051(+)	`GCCTAA/GCTGTC`	1	--	us2k¹		0	--	--	--	--
rs11752388^1,2	C,H	--	108879588(+)	`CTCGAT/ATGTTT`	1	--	us2k¹ tfbs³		5		NS EA NA	414
rs145562362^1,2		--	108879829(+)	`GGGCGA/CTGCGC`	1	--	us2k¹		0	--	--	--	--
rs147292299^1,2		--	108879905(+)	`TGTATC/GGGGTC`	1	--	us2k¹		0	--	--	--	--
rs80231243^1,2		--	108880013(+)	`GCATGC/TCGCGT`	1	--	us2k¹		0	--	--	--	--
rs28396961^1,2	C	--	108880104(+)	`ACCTAA/GAGGAT`	2	--	us2k¹		1		NA	2
rs74447671^1,2	C,F,	--	108880154(+)	`TTTGTC/TGTCAT`	2	--	us2k¹		3		NA	124
rs182733567^1,2		--	108880262(+)	`TACACC/TTCTCC`	2	--	us2k¹		0	--	--	--	--
rs149794853^1,2		--	108880444(+)	`CTGCCC/TATCTT`	2	--	us2k¹		0	--	--	--	--
rs72940666^1,2	C,F,	--	108880487(+)	`TGTCGC/TGTTCT`	2	--	us2k¹		2		WA EA	238

HapMap Linkage Disequilibrium report for FOXO3 (108881026 - 109005977 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 3 variations for FOXO3
3 CNVs: 99661 69587 36446

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

FOXO3 for disorders About GeneDecksing

OMIM gene information: 602681 OMIM disorders: --

UniProtKB/Swiss-Prot: FOXO3_HUMAN, O43524

Note=A chromosomal aberration involving FOXO3 is found in secondary acute leukemias. Translocation

t(6;11)(q21;q23) with MLL/HRX

20/64 diseases for FOXO3 (see all 64): About MalaCards

rhabdomyosarcoma acute leukemia leukemia cleft lip/palate

anaplastic large cell lymphoma cleft lip non-hodgkin lymphoma squamous cell carcinoma

premature ovarian failure lupus erythematosus myeloid leukemia oral squamous cell carcinoma

esophageal squamous cell carcinoma systemic lupus erythematosus differentiating neuroblastoma hodgkin's lymphoma

chronic lymphocytic leukemia muscular atrophy neurodegenerative disease chronic myeloid leukemia

10/12 Novoseek disease relationships for FOXO3 gene (see all 12) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
rhabdomyosarcoma	36.1	1	12196101 (1)
breast cancer	33.2	30	20371610 (4), 18312651 (4), 17575143 (4), 14527951 (3) (see all 12)
prostate cancer	32.2	11	12351634 (3), 17522055 (2), 15798096 (2), 17563745 (1) (see all 5)
tumors	31.3	28	15551757 (3), 15084260 (2), 19564415 (2), 18312651 (2) (see all 14)
cancer	29	10	19564415 (2), 20484037 (2), 19911116 (1), 18239069 (1) (see all 8)
leukemia	24.7	2	11278373 (1), 18055337 (1)
myeloid leukemia chronic	17	4	17900262 (1), 12456669 (1), 18644865 (1)
necrosis	6.84	4	17900262 (1), 18166693 (1), 19473970 (1), 15322085 (1)
lupus erythematosus systemic	0	2	17873969 (1), 18045156 (1)
neovascularization	0	1	16100571 (1)

Human Genome Epidemiology (HuGE) Navigator: FOXO3 (3 documents)

Export disorders for FOXO3 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for FOXO3 gene, integrated from 9 sources (see all 365):
(articles sorted by number of sources associating them with FOXO3)

Utopia: connect your pdf to the dynamic
world of online information

Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily. (PubMed id 9479491)^{1, 2, 3, 9} Anderson M.J.... Arden K.C. (1998)
Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a). (PubMed id 11154281)^{1, 2, 9} Brunet A.... Greenberg M.E. (2001)
Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. (PubMed id 10102273)^{1, 2, 9} Brunet A.... Greenberg M.E. (1999)
Methylation by Set9 modulates FoxO3 stability and transcriptional activity. (PubMed id 22820736)^{1, 2} Calnan D.R.... Brunet A. (2012)
Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels. (PubMed id 18593906)^{1, 2} Morishita D.... Fujita N. (2008)
Crystal structure of the human FOXO3a-DBD/DNA complex suggests the effects of post-translational modification. (PubMed id 17940099)^{1, 2} Tsai K.-L....Hsiao C.-D. (2007)
The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO3 transcription factor. (PubMed id 17711846)^{1, 2} Greer E.L....Brunet A. (2007)
A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. (PubMed id 16751106)^{1, 2} Lehtinen M.K.... Bonni A. (2006)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)^{1, 2} Gerhard D.S....Malek J. (2004)
The DNA sequence and analysis of human chromosome 6. (PubMed id 14574404)^{1, 2} Mungall A.J.... Beck S. (2003)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 2309	HGNC: 3821	AceView: FOXO3A	Ensembl:ENSG00000118689	euGenes: HUgn2309
ECgene: FOXO3	Kegg: 2309	H-InvDB: FOXO3

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for FOXO3	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for FOXO3	Genetics and Cytogenetics in Oncology and Haematology

Intellectual Property for FOXO3 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for FOXO3 gene:
Search GeneIP for patents involving FOXO3

Licensable Technologies for FOXO3 gene:

Salk Institute:

Increasing Life Span by Modulation of the Smek Gene

GeneCards and IP:
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