DegronMD - Q01167(FOXK2)

FUNCTION: Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis 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:22083952, PubMed:25451922). Together with FOXK1, 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). Together with FOXK1, 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). In addition to the 5'-GTAAACA-3' DNA motif, also binds the 5'-TGANTCA-3' palindromic DNA motif, and co-associates with JUN/AP-1 to activate transcription (PubMed:22083952). Also able to bind to a minimal DNA heteroduplex containing a G/T-mismatch with 5'-TRT[G/T]NB-3' sequence (PubMed:20097901). Binds to NFAT-like motifs (purine-rich) in the IL2 promoter (PubMed:1339390). Positively regulates WNT/beta-catenin signaling by translocating DVL proteins into the nucleus (PubMed:25805136). Also binds to HIV-1 long terminal repeat. May be involved in both positive and negative regulation of important viral and cellular promoter elements (PubMed:1909027). {ECO:0000250|UniProtKB:Q3UCQ1, ECO:0000269|PubMed:1339390, ECO:0000269|PubMed:1909027, ECO:0000269|PubMed:20097901, ECO:0000269|PubMed:22083952, ECO:0000269|PubMed:25451922, ECO:0000269|PubMed:25805136}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.L362M	TCGA-29-1698	OV	TCGA	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation altering degron motif	0.711
p.L362M	TCGA-FS-A1Z0	SKCM	TCGA	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation altering degron motif	0.711
p.L362M	DO28531	OV	ICGC	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation altering degron motif	0.711
p.L362M	DO37431	SKCM	ICGC	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation altering degron motif	0.711
p.A446S	TCGA-55-7911	LUAD	TCGA	VATPVTT	DEG_SCF_FBW7_1	454:460	Mutation rewiring degron network	0.1111
p.A446S	DO24821	LUAD	ICGC	VATPVTT	DEG_SCF_FBW7_1	454:460	Mutation rewiring degron network	0.1111
p.R359K	TCGA-AP-A1E0	UCEC	TCGA	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation altering degron motif	0.7237
p.R359K	DO43154	UCEC	ICGC	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation altering degron motif	0.7237
p.P364L	TCGA-CK-5916	COAD	TCGA	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation altering degron motif	0.6471
p.P364L	DO8786	COAD	ICGC	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation altering degron motif	0.6471
p.T360I	TCGA-D3-A8GR	SKCM	TCGA	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation altering degron motif	0.7078
p.T360I	TCGA-FS-A1ZZ	SKCM	TCGA	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation altering degron motif	0.7078
p.T360I	DO37412	SKCM	ICGC	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation altering degron motif	0.7078
p.T360I	DO51247	SKCM	ICGC	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation altering degron motif	0.7078
p.P361S	TCGA-DA-A95Z	SKCM	TCGA	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation altering degron motif	0.5641
p.P361S	DO219481	SKCM	ICGC	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation altering degron motif	0.5641
p.P374H	TCGA-EE-A2MD	SKCM	TCGA	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation rewiring degron network	0.1111
p.P374H	DO37851	SKCM	ICGC	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation rewiring degron network	0.1111
p.R353S	TCGA-ER-A19G	SKCM	TCGA	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation rewiring degron network	0.1944
p.R353S	DO47284	SKCM	ICGC	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation rewiring degron network	0.1944
p.L362V	DO224618	BRCA	ICGC	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation altering degron motif	0.6765
p.L362V	DO1016	BRCA	ICGC	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation altering degron motif	0.6765
p.Q445L	DO3182	BRCA	ICGC	VATPVTT	DEG_SCF_FBW7_1	454:460	Mutation rewiring degron network	0.0833
p.V355M	DO220910	MELA	ICGC	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation rewiring degron network	0.25
p.V355M	SIDM01043	Other Sarcomas	GDSC	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation rewiring degron network	0.25
p.P449H	DO46591	OV	ICGC	VATPVTT	DEG_SCF_FBW7_1	454:460	Mutation rewiring degron network	0.1944
p.P449H	DO46591	OV	ICGC	PVTTS	DEG_SPOP_SBC_1	457:461	Mutation rewiring degron network	0.1111
p.S461L	SIDM00108	Melanoma	GDSC	PVTTS	DEG_SPOP_SBC_1	457:461	Mutation altering degron motif	0.7667
p.S461L	SIDM00652	Small Cell Lung Carcinoma	GDSC	PVTTS	DEG_SPOP_SBC_1	457:461	Mutation altering degron motif	0.7667
p.A372T	SIDM00220	Ovarian Carcinoma	GDSC	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation rewiring degron network	0.1667
p.A372T	ACH-000962	Ovarian Cancer	CCLE	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation rewiring degron network	0.1667
p.A372T	ACH-001145	Ovarian Cancer	CCLE	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation rewiring degron network	0.1667
p.A372T	OC-314	ovary	COSMIC	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation rewiring degron network	0.1667
p.L365F	SIDM01609	Endometrial Carcinoma	GDSC	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation altering degron motif	0.6981
p.L365F	ACH-000972	Endometrial/Uterine Cancer	CCLE	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation altering degron motif	0.6981
p.R353M	SIDM01451	Pancreatic Carcinoma	GDSC	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation rewiring degron network	0.1944
p.R353M	ACH-000933	Pancreatic Cancer	CCLE	FRTPLGPLS	DEG_APCC_DBOX_1	358:366	Mutation rewiring degron network	0.1944

Kaplan plot for FOXK2 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

FOXK2

UniProt ID: Q01167

Entrez ID: 3607

Protein name: Forkhead box protein K2 (G/T-mismatch specific binding protein) (nGTBP) (Interleukin enhancer-binding factor 1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for FOXK2 in