DegronMD - P85037(FOXK1)

FUNCTION: Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis, muscle cell differentiation and autophagy (By similarity). Recognizes and binds the forkhead DNA sequence motif (5'-GTAAACA-3') and can both act as a transcription activator or repressor, depending on the context (PubMed:17670796). Together with FOXK2, acts as a key regulator of metabolic reprogramming towards aerobic glycolysis, a process in which glucose is converted to lactate in the presence of oxygen (By similarity). Acts by promoting expression of enzymes for glycolysis (such as hexokinase-2 (HK2), phosphofructokinase, pyruvate kinase (PKLR) and lactate dehydrogenase), while suppressing further oxidation of pyruvate in the mitochondria by up-regulating pyruvate dehydrogenase kinases PDK1 and PDK4 (By similarity). Probably plays a role in gluconeogenesis during overnight fasting, when lactate from white adipose tissue and muscle is the main substrate (By similarity). Involved in mTORC1-mediated metabolic reprogramming: in response to mTORC1 signaling, translocates into the nucleus and regulates the expression of genes associated with glycolysis and downstream anabolic pathways, such as HIF1A, thereby regulating glucose metabolism (By similarity). Together with FOXK2, acts as a negative regulator of autophagy in skeletal muscle: in response to starvation, enters the nucleus, binds the promoters of autophagy genes and represses their expression, preventing proteolysis of skeletal muscle proteins (By similarity). Acts as a transcriptional regulator of the myogenic progenitor cell population in skeletal muscle (By similarity). Binds to the upstream enhancer region (CCAC box) of myoglobin (MB) gene, regulating the myogenic progenitor cell population (By similarity). Promotes muscle progenitor cell proliferation by repressing the transcriptional activity of FOXO4, thereby inhibiting myogenic differentiation (By similarity). Involved in remodeling processes of adult muscles that occur in response to physiological stimuli (By similarity). Required to correct temporal orchestration of molecular and cellular events necessary for muscle repair (By similarity). Represses myogenic differentiation by inhibiting MEFC activity (By similarity). Positively regulates Wnt/beta-catenin signaling by translocating DVL into the nucleus (PubMed:25805136). Reduces virus replication, probably by binding the interferon stimulated response element (ISRE) to promote antiviral gene expression (PubMed:25852164). {ECO:0000250|UniProtKB:P42128, ECO:0000269|PubMed:17670796, ECO:0000269|PubMed:25805136, ECO:0000269|PubMed:25852164}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.G260C	TCGA-43-2581	LUSC	TCGA	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.3056
p.G260C	DO229035	LICA	ICGC	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.3056
p.G260C	DO26602	LUSC	ICGC	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.3056
p.P251L	TCGA-A3-3357	KIRC	TCGA	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.0556
p.P251L	DO20396	KIRC	ICGC	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.0556
p.V522I	TCGA-A6-6781	COAD	TCGA	VVTTS	DEG_SPOP_SBC_1	527:531	Mutation rewiring degron network	0.1944
p.V522I	TCGA-OR-A5J5	ACC	TCGA	VVTTS	DEG_SPOP_SBC_1	527:531	Mutation rewiring degron network	0.1944
p.V522I	DO8447	COAD	ICGC	VVTTS	DEG_SPOP_SBC_1	527:531	Mutation rewiring degron network	0.1944
p.R259C	TCGA-AD-6888	COAD	TCGA	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.2778
p.R259C	DO10435	COAD	ICGC	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.2778
p.V525I	TCGA-AP-A0LM	UCEC	TCGA	VVTTS	DEG_SPOP_SBC_1	527:531	Mutation rewiring degron network	0.2778
p.V525I	DO43306	UCEC	ICGC	VVTTS	DEG_SPOP_SBC_1	527:531	Mutation rewiring degron network	0.2778
p.Q518R	TCGA-BG-A222	UCEC	TCGA	VVTTS	DEG_SPOP_SBC_1	527:531	Mutation rewiring degron network	0.0833
p.Q518R	DO42977	UCEC	ICGC	VVTTS	DEG_SPOP_SBC_1	527:531	Mutation rewiring degron network	0.0833
p.V525G	TCGA-DD-A1EC	LIHC	TCGA	VVTTS	DEG_SPOP_SBC_1	527:531	Mutation rewiring degron network	0.2778
p.V525G	DO22982	LIHC	ICGC	VVTTS	DEG_SPOP_SBC_1	527:531	Mutation rewiring degron network	0.2778
p.S253F	TCGA-EE-A180	SKCM	TCGA	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation blocking phosphorylation signal	0.5556
p.S253F	DO47537	SKCM	ICGC	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation blocking phosphorylation signal	0.5556
p.S253F	SIDM01629	Melanoma	GDSC	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation blocking phosphorylation signal	0.5556
p.S253F	ACH-000404	Skin Cancer	CCLE	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation blocking phosphorylation signal	0.5556
p.P258L	TCGA-EE-A2GR	SKCM	TCGA	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.25
p.P258L	DO37996	SKCM	ICGC	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.25
p.T530I	TCGA-L5-A4OJ	ESCA	TCGA	VVTTS	DEG_SPOP_SBC_1	527:531	Mutation altering degron motif	0.7078
p.A519P	TCGA-SL-A6JA	UCEC	TCGA	VVTTS	DEG_SPOP_SBC_1	527:531	Mutation rewiring degron network	0.1111
p.A519P	DO219787	UCEC	ICGC	VVTTS	DEG_SPOP_SBC_1	527:531	Mutation rewiring degron network	0.1111
p.S257I	DO228952	LICA	ICGC	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation blocking phosphorylation signal	0.6667
p.A532S	DO229018	LICA	ICGC	VVTTS	DEG_SPOP_SBC_1	527:531	Mutation rewiring degron network	0.3056
p.A261V	DO229051	LICA	ICGC	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation altering degron motif	0.5825
p.C254W	SIDM00120	Prostate Carcinoma	GDSC	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.1389
p.C254W	ACH-000979	Prostate Cancer	CCLE	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.1389
p.C254W	DU-145	prostate	COSMIC	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.1389
p.V269M	SIDM00789	Colorectal Carcinoma	GDSC	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.2222
p.V269M	ACH-000997	Colon/Colorectal Cancer	CCLE	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.2222
p.V269M	HCT-15	large intestine	COSMIC	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.2222
p.N271S	SIDM00217	Colorectal Carcinoma	GDSC	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.1667
p.N271S	ACH-000999	Colon/Colorectal Cancer	CCLE	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.1667
p.N271S	SNU-1040	large intestine	COSMIC	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.1667
p.D275E	SIDM00921	Non-Small Cell Lung Carcinoma	GDSC	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.0556
p.D275E	ACH-000264	Lung Cancer	CCLE	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.0556
p.D275E	Calu-6	lung	COSMIC	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation rewiring degron network	0.0556
p.S534L	SIDM00839	Colorectal Carcinoma	GDSC	VVTTS	DEG_SPOP_SBC_1	527:531	Mutation rewiring degron network	0.25
p.S534L	ACH-000950	Colon/Colorectal Cancer	CCLE	VVTTS	DEG_SPOP_SBC_1	527:531	Mutation rewiring degron network	0.25
p.S263F	SIDM00937	Oral Cavity Carcinoma	GDSC	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation altering degron motif	0.7982
p.S263F	ACH-000832	Head and Neck Cancer	CCLE	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation altering degron motif	0.7982
p.S263F	CAL-27	upper aerodigestive tract	COSMIC	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation altering degron motif	0.7982
p.G537R	SIDM01450	Gastric Carcinoma	GDSC	VVTTS	DEG_SPOP_SBC_1	527:531	Mutation rewiring degron network	0.1667
p.G537R	ACH-000898	Gastric Cancer	CCLE	VVTTS	DEG_SPOP_SBC_1	527:531	Mutation rewiring degron network	0.1667
p.G262S	ACH-001354	Neuroblastoma	CCLE	AGSSS	DEG_SPOP_SBC_1	261:265	Mutation altering degron motif	0.5882

Kaplan plot for FOXK1 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

FOXK1

UniProt ID: P85037

Entrez ID: 221937

Protein name: Forkhead box protein K1 (Myocyte nuclear factor) (MNF)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for FOXK1 in