DegronMD - Q9BZS1(FOXP3)

FUNCTION: Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg) (PubMed:17377532, PubMed:21458306, PubMed:30513302, PubMed:23947341, PubMed:24354325, PubMed:24722479, PubMed:24835996). Plays an essential role in maintaining homeostasis of the immune system by allowing the acquisition of full suppressive function and stability of the Treg lineage, and by directly modulating the expansion and function of conventional T-cells (PubMed:23169781). Can act either as a transcriptional repressor or a transcriptional activator depending on its interactions with other transcription factors, histone acetylases and deacetylases (PubMed:17377532, PubMed:21458306, PubMed:23947341, PubMed:24354325, PubMed:24722479). The suppressive activity of Treg involves the coordinate activation of many genes, including CTLA4 and TNFRSF18 by FOXP3 along with repression of genes encoding cytokines such as interleukin-2 (IL2) and interferon-gamma (IFNG) (PubMed:17377532, PubMed:21458306, PubMed:23947341, PubMed:24354325, PubMed:24722479). Inhibits cytokine production and T-cell effector function by repressing the activity of two key transcription factors, RELA and NFATC2 (PubMed:15790681). Mediates transcriptional repression of IL2 via its association with histone acetylase KAT5 and histone deacetylase HDAC7 (PubMed:17360565). Can activate the expression of TNFRSF18, IL2RA and CTLA4 and repress the expression of IL2 and IFNG via its association with transcription factor RUNX1 (PubMed:17377532). Inhibits the differentiation of IL17 producing helper T-cells (Th17) by antagonizing RORC function, leading to down-regulation of IL17 expression, favoring Treg development (PubMed:18368049). Inhibits the transcriptional activator activity of RORA (PubMed:18354202). Can repress the expression of IL2 and IFNG via its association with transcription factor IKZF4 (By similarity). {ECO:0000250|UniProtKB:Q99JB6, ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:17360565, ECO:0000269|PubMed:17377532, ECO:0000269|PubMed:18354202, ECO:0000269|PubMed:18368049, ECO:0000269|PubMed:21458306, ECO:0000269|PubMed:23169781, ECO:0000269|PubMed:24835996, ECO:0000269|PubMed:30513302, ECO:0000303|PubMed:23947341, ECO:0000303|PubMed:24354325, ECO:0000303|PubMed:24722479}. View more >>

GO - Biological processes (BP): B cell homeostasis [GO:0001782]; CD4-positive, CD25-positive, alpha-beta regulatory T cell lineage commitment [GO:0002362]; chromatin remodeling [GO:0006338]; establishment of endothelial blood-brain barrier [GO:0014045]; gene expression [GO:0010467]; myeloid cell homeostasis [GO:0002262]; negative regulation of activated T cell proliferation [GO:0046007]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of chronic inflammatory response [GO:0002677]; negative regulation of CREB transcription factor activity [GO:0032792]; negative regulation of cytokine production [GO:0001818]; negative regulation of defense response to virus [GO:0050687]; negative regulation of DNA-binding transcription factor activity [GO:0043433]; negative regulation of histone acetylation [GO:0035067]; negative regulation of histone deacetylation [GO:0031064]; negative regulation of immune response [GO:0050777]; negative regulation of interferon-gamma production [GO:0032689]; negative regulation of interleukin-10 production [GO:0032693]; negative regulation of interleukin-17 production [GO:0032700]; negative regulation of interleukin-2 production [GO:0032703]; negative regulation of interleukin-4 production [GO:0032713]; negative regulation of interleukin-5 production [GO:0032714]; negative regulation of interleukin-6 production [GO:0032715]; negative regulation of isotype switching to IgE isotypes [GO:0048294]; negative regulation of NF-kappaB transcription factor activity [GO:0032088]; negative regulation of T cell cytokine production [GO:0002725]; negative regulation of T cell proliferation [GO:0042130]; negative regulation of T-helper 17 cell differentiation [GO:2000320]; negative regulation of transcription, DNA-templated [GO:0045892]; negative regulation of transcription by RNA polymerase II [GO:0000122]; negative regulation of tumor necrosis factor production [GO:0032720]; positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation [GO:0032831]; positive regulation of histone acetylation [GO:0035066]; positive regulation of immature T cell proliferation in thymus [GO:0033092]; positive regulation of interleukin-4 production [GO:0032753]; positive regulation of peripheral T cell tolerance induction [GO:0002851]; positive regulation of regulatory T cell differentiation [GO:0045591]; positive regulation of T cell anergy [GO:0002669]; positive regulation of transcription, DNA-templated [GO:0045893]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of transforming growth factor beta1 production [GO:0032914]; regulation of isotype switching to IgG isotypes [GO:0048302]; regulation of T cell anergy [GO:0002667]; regulation of transcription, DNA-templated [GO:0006355]; regulation of transcription by RNA polymerase II [GO:0006357]; response to lipopolysaccharide [GO:0032496]; response to radiation [GO:0009314]; response to rapamycin [GO:1901355]; response to virus [GO:0009615]; T cell activation [GO:0042110]; T cell homeostasis [GO:0043029]; T cell mediated immunity [GO:0002456]; T cell receptor signaling pathway [GO:0050852]; tolerance induction to self antigen [GO:0002513] 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.S125I	TCGA-06-1801	GBM	TCGA	ISLTPPTT	DEG_SCF_FBW7_1	129:136	Mutation rewiring degron network	0.2222
p.R146Q	TCGA-B5-A3FA	UCEC	TCGA	ISLTPPTT	DEG_SCF_FBW7_1	129:136	Mutation rewiring degron network	0.0556
p.R146W	TCGA-FR-A726	SKCM	TCGA	ISLTPPTT	DEG_SCF_FBW7_1	129:136	Mutation rewiring degron network	0.0556
p.G52V	DO225362	BRCA	ICGC	ASSSS	DEG_SPOP_SBC_1	56:60	Mutation rewiring degron network	0.2222
p.G52V	DO228483	BRCA	ICGC	ASSSS	DEG_SPOP_SBC_1	56:60	Mutation rewiring degron network	0.2222
p.G52V	DO231191	LUSC	ICGC	ASSSS	DEG_SPOP_SBC_1	56:60	Mutation rewiring degron network	0.2222
p.G52V	SIDM00993	Plasma Cell Myeloma	GDSC	ASSSS	DEG_SPOP_SBC_1	56:60	Mutation rewiring degron network	0.2222
p.G52V	SIDM01038	B-Cell Non-Hodgkin's Lymphoma	GDSC	ASSSS	DEG_SPOP_SBC_1	56:60	Mutation rewiring degron network	0.2222
p.N62K	DO229029	LICA	ICGC	ASSSS	DEG_SPOP_SBC_1	56:60	Mutation rewiring degron network	0.2778
p.A141E	DO229006	LICA	ICGC	ISLTPPTT	DEG_SCF_FBW7_1	129:136	Mutation rewiring degron network	0.1944
p.Q70K	DO228346	MALY	ICGC	ASSSS	DEG_SPOP_SBC_1	56:60	Mutation rewiring degron network	0.0556
p.M64T	DO34841	PACA	ICGC	ASSSS	DEG_SPOP_SBC_1	56:60	Mutation rewiring degron network	0.2222
p.R143K	DO37436	SKCM	ICGC	ISLTPPTT	DEG_SCF_FBW7_1	129:136	Mutation rewiring degron network	0.1389
p.D49H	ACH-000521	Lung Cancer	CCLE	ASSSS	DEG_SPOP_SBC_1	56:60	Mutation rewiring degron network	0.1389
p.P65T	ACH-000779	Lung Cancer	CCLE	ASSSS	DEG_SPOP_SBC_1	56:60	Mutation rewiring degron network	0.1944
p.M64I	ACH-000779	Lung Cancer	CCLE	ASSSS	DEG_SPOP_SBC_1	56:60	Mutation rewiring degron network	0.2222
p.P142H	HT-29	large intestine	COSMIC	ISLTPPTT	DEG_SCF_FBW7_1	129:136	Mutation blocking phosphorylation signal	0.6111
p.P127H	HT-29	large intestine	COSMIC	ISLTPPTT	DEG_SCF_FBW7_1	129:136	Mutation rewiring degron network	0.2778

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

FOXP3

UniProt ID: Q9BZS1

Entrez ID: 50943

Protein name: Forkhead box protein P3 (Scurfin) [Cleaved into: Forkhead box protein P3, C-terminally processed; Forkhead box protein P3 41 kDa form]

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for FOXP3 in