DegronMD - Q12778(FOXO1)

FUNCTION: Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress (PubMed:10358076, PubMed:12228231, PubMed:15220471, PubMed:15890677, PubMed:18356527, PubMed:19221179, PubMed:20543840, PubMed:21245099). Binds to the insulin response element (IRE) with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with consensus sequence 5'-TT[G/A]TTTAC-3' (PubMed:10358076). Activity suppressed by insulin (PubMed:10358076). Main regulator of redox balance and osteoblast numbers and controls bone mass (By similarity). Orchestrates the endocrine function of the skeleton in regulating glucose metabolism (By similarity). Also acts as a key regulator of chondrogenic commitment of skeletal progenitor cells in response to lipid availability: when lipids levels are low, translocates to the nucleus and promotes expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (By similarity). Acts synergistically with ATF4 to suppress osteocalcin/BGLAP activity, increasing glucose levels and triggering glucose intolerance and insulin insensitivity (By similarity). Also suppresses the transcriptional activity of RUNX2, an upstream activator of osteocalcin/BGLAP (By similarity). Acts as an inhibitor of glucose sensing in pancreatic beta cells by acting as a transcription repressor and suppressing expression of PDX1 (By similarity). In hepatocytes, promotes gluconeogenesis by acting together with PPARGC1A and CEBPA to activate the expression of genes such as IGFBP1, G6PC1 and PCK1 (By similarity). Also promotes gluconeogenesis by directly promoting expression of PPARGC1A and G6PC1 (PubMed:17024043). Important regulator of cell death acting downstream of CDK1, PKB/AKT1 and STK4/MST1 (PubMed:18356527, PubMed:19221179). Promotes neural cell death (PubMed:18356527). Mediates insulin action on adipose tissue (By similarity). Regulates the expression of adipogenic genes such as PPARG during preadipocyte differentiation and, adipocyte size and adipose tissue-specific gene expression in response to excessive calorie intake (By similarity). Regulates the transcriptional activity of GADD45A and repair of nitric oxide-damaged DNA in beta-cells (By similarity). Required for the autophagic cell death induction in response to starvation or oxidative stress in a transcription-independent manner (PubMed:20543840). Mediates the function of MLIP in cardiomyocytes hypertrophy and cardiac remodeling (By similarity). Regulates endothelial cell (EC) viability and apoptosis in a PPIA/CYPA-dependent manner via transcription of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (PubMed:31063815). {ECO:0000250|UniProtKB:A4L7N3, ECO:0000250|UniProtKB:G3V7R4, ECO:0000250|UniProtKB:Q9R1E0, ECO:0000269|PubMed:10358076, ECO:0000269|PubMed:12228231, ECO:0000269|PubMed:15220471, ECO:0000269|PubMed:15890677, ECO:0000269|PubMed:17024043, ECO:0000269|PubMed:18356527, ECO:0000269|PubMed:19221179, ECO:0000269|PubMed:20543840, ECO:0000269|PubMed:21245099, ECO:0000269|PubMed:31063815}. View more >>

GO - Biological processes (BP): View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.W310L	TCGA-05-4427	LUAD	TCGA	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.1944
p.W310L	DO23666	LUAD	ICGC	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.1944
p.S406L	TCGA-90-A4ED	LUSC	TCGA	MQQTPCYS	DEG_SCF_FBW7_1	399:406	Mutation altering degron motif	0.7667
p.S406L	DO45482	LUSC	ICGC	MQQTPCYS	DEG_SCF_FBW7_1	399:406	Mutation altering degron motif	0.7667
p.S329L	TCGA-94-7943	LUSC	TCGA	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation blocking phosphorylation signal	0.5
p.S329L	DO26475	LUSC	ICGC	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation blocking phosphorylation signal	0.5
p.T402M	TCGA-A5-A1OF	UCEC	TCGA	MQQTPCYS	DEG_SCF_FBW7_1	399:406	Mutation altering degron motif	0.8534
p.T402M	DO42568	UCEC	ICGC	MQQTPCYS	DEG_SCF_FBW7_1	399:406	Mutation altering degron motif	0.8534
p.R316Q	TCGA-AN-A046	BRCA	TCGA	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation altering degron motif	0.6218
p.R316Q	TCGA-EO-A22R	UCEC	TCGA	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation altering degron motif	0.6218
p.R316Q	DO1285	BRCA	ICGC	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation altering degron motif	0.6218
p.R316Q	DO42713	UCEC	ICGC	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation altering degron motif	0.6218
p.R316Q	SIDM01943	Colorectal Carcinoma	GDSC	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation altering degron motif	0.6218
p.R314H	TCGA-AX-A06F	UCEC	TCGA	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.3056
p.R314H	TCGA-B5-A3FC	UCEC	TCGA	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.3056
p.R314H	TCGA-F5-6814	READ	TCGA	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.3056
p.R314H	TCGA-XK-AAIW	PRAD	TCGA	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.3056
p.R314H	DO51407	PRAD	ICGC	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.3056
p.R314H	DO36556	READ	ICGC	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.3056
p.R314H	DO41752	UCEC	ICGC	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.3056
p.R314H	DO41871	UCEC	ICGC	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.3056
p.F313V	TCGA-B5-A3FA	UCEC	TCGA	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.2778
p.F313V	DO52402	UCEC	ICGC	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.2778
p.L414S	TCGA-BT-A2LB	BLCA	TCGA	MQQTPCYS	DEG_SCF_FBW7_1	399:406	Mutation rewiring degron network	0.1111
p.L414S	DO44098	BLCA	ICGC	MQQTPCYS	DEG_SCF_FBW7_1	399:406	Mutation rewiring degron network	0.1111
p.G326R	TCGA-CJ-4913	KIRC	TCGA	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.1389
p.G326R	DO20377	KIRC	ICGC	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.1389
p.A408T	TCGA-D1-A0ZO	UCEC	TCGA	MQQTPCYS	DEG_SCF_FBW7_1	399:406	Mutation rewiring degron network	0.2778
p.A408T	DO41927	UCEC	ICGC	MQQTPCYS	DEG_SCF_FBW7_1	399:406	Mutation rewiring degron network	0.2778
p.R314C	TCGA-D1-A17Q	UCEC	TCGA	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.3056
p.R314C	TCGA-D3-A51G	SKCM	TCGA	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.3056
p.R314C	TCGA-F4-6570	COAD	TCGA	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.3056
p.R314C	DO10443	COAD	ICGC	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.3056
p.R314C	DO47700	SKCM	ICGC	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.3056
p.R314C	DO41903	UCEC	ICGC	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.3056
p.A408V	TCGA-E6-A1LX	UCEC	TCGA	MQQTPCYS	DEG_SCF_FBW7_1	399:406	Mutation rewiring degron network	0.2778
p.A408V	TCGA-HU-A4GU	STAD	TCGA	MQQTPCYS	DEG_SCF_FBW7_1	399:406	Mutation rewiring degron network	0.2778
p.A408V	DO47849	STAD	ICGC	MQQTPCYS	DEG_SCF_FBW7_1	399:406	Mutation rewiring degron network	0.2778
p.A408V	DO41020	UCEC	ICGC	MQQTPCYS	DEG_SCF_FBW7_1	399:406	Mutation rewiring degron network	0.2778
p.G326V	TCGA-EE-A181	SKCM	TCGA	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.1389
p.G326V	DO37444	SKCM	ICGC	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.1389
p.T323A	TCGA-FS-A1ZZ	SKCM	TCGA	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation blocking phosphorylation signal	0.6667
p.T323A	DO37412	SKCM	ICGC	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation blocking phosphorylation signal	0.6667
p.N309S	DO48424	BLCA	ICGC	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.1667
p.P403S	DO11854	GBM	ICGC	MQQTPCYS	DEG_SCF_FBW7_1	399:406	Mutation altering degron motif	0.6752
p.P410Q	DO229015	LICA	ICGC	MQQTPCYS	DEG_SCF_FBW7_1	399:406	Mutation rewiring degron network	0.2222
p.Q392K	DO229029	LICA	ICGC	MQQTPCYS	DEG_SCF_FBW7_1	399:406	Mutation rewiring degron network	0.1389
p.P409T	DO229045	LICA	ICGC	MQQTPCYS	DEG_SCF_FBW7_1	399:406	Mutation rewiring degron network	0.25
p.P409Q	DO229009	LICA	ICGC	MQQTPCYS	DEG_SCF_FBW7_1	399:406	Mutation rewiring degron network	0.25
p.N309D	SIDM00537	Colorectal Carcinoma	GDSC	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.1667
p.N309D	ACH-000982	Colon/Colorectal Cancer	CCLE	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.1667
p.N309D	ACH-001345	Colon/Colorectal Cancer	CCLE	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.1667
p.N309D	GP5d	large intestine	COSMIC	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation rewiring degron network	0.1667
p.S325T	ACH-001737	Leukemia	CCLE	PRTSS	DEG_SPOP_SBC_1	315:319	Mutation blocking phosphorylation signal	0.6111

Kaplan plot for FOXO1 in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

FOXO1

UniProt ID: Q12778

Entrez ID: 2308

Protein name: Forkhead box protein O1 (Forkhead box protein O1A) (Forkhead in rhabdomyosarcoma)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for FOXO1 in