DegronMD - P19484(TFEB)

FUNCTION: Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response (PubMed:21617040, PubMed:22576015, PubMed:22343943, PubMed:22692423, PubMed:30120233, PubMed:31672913). Specifically recognizes and binds E-box sequences (5'-CANNTG-3'); efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFE3 or MITF (PubMed:1748288, PubMed:19556463, PubMed:29146937). Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, TFEB phosphorylation by MTOR promotes its cytosolic retention and subsequent inactivation (PubMed:21617040, PubMed:22576015, PubMed:22343943, PubMed:22692423). Upon starvation or lysosomal stress, inhibition of MTOR induces TFEB dephosphorylation, resulting in nuclear localization and transcription factor activity (PubMed:22576015, PubMed:22343943, PubMed:22692423). Specifically recognizes and binds the CLEAR-box sequence (5'-GTCACGTGAC-3') present in the regulatory region of many lysosomal genes, leading to activate their expression, thereby playing a central role in expression of lysosomal genes (PubMed:19556463, PubMed:22692423). Regulates lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1 (PubMed:29146937). Acts as a positive regulator of autophagy by promoting expression of genes involved in autophagy (PubMed:21617040, PubMed:22576015, PubMed:23434374, PubMed:27278822). In association with TFE3, activates the expression of CD40L in T-cells, thereby playing a role in T-cell-dependent antibody responses in activated CD4(+) T-cells and thymus-dependent humoral immunity (By similarity). Specifically recognizes the gamma-E3 box, a subset of E-boxes, present in the heavy-chain immunoglobulin enhancer (PubMed:2115126). Plays a role in the signal transduction processes required for normal vascularization of the placenta (By similarity). Involved in the immune response to infection by the bacteria S.aureus or S.enterica, acting downstream of protein kinase D (PKD), probably by regulating cytokine and chemokine expression (By similarity). {ECO:0000250|UniProtKB:Q9R210, ECO:0000269|PubMed:1748288, ECO:0000269|PubMed:19556463, ECO:0000269|PubMed:2115126, ECO:0000269|PubMed:21617040, ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23434374, ECO:0000269|PubMed:27278822, ECO:0000269|PubMed:29146937, ECO:0000269|PubMed:30120233, ECO:0000269|PubMed:31672913}. View more >>

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

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

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

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Open in full screen with detailed sequence annotations

Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.G124V	TCGA-55-A48X	LUAD	TCGA	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.1667
p.G124V	DO24048	LUAD	ICGC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.1667
p.L204M	TCGA-86-7701	LUAD	TCGA	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation rewiring degron network	0.25
p.L204M	TCGA-86-7701	LUAD	TCGA	NVYSSDP	CBL_PTK	192:198	Mutation rewiring degron network	0.1667
p.P411L	TCGA-AJ-A3BH	UCEC	TCGA	PPGY	ITCH	410:413	Mutation altering degron motif	0.7582
p.P411L	DO227695	PACA	ICGC	PPGY	ITCH	410:413	Mutation altering degron motif	0.7582
p.P411L	DO41638	UCEC	ICGC	PPGY	ITCH	410:413	Mutation altering degron motif	0.7582
p.A135T	TCGA-AP-A1DK	UCEC	TCGA	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.3056
p.A135T	DO233766	GACA	ICGC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.3056
p.A135T	DO36801	READ	ICGC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.3056
p.A135T	DO42033	UCEC	ICGC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.3056
p.A135T	ACH-001049	Lung Cancer	CCLE	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.3056
p.A135T	ACH-002272	Lymphoma	CCLE	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.3056
p.A135T	CPC-N	lung	COSMIC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.3056
p.A135T	MHH-PREB-1	haematopoietic and lymphoid tissue	COSMIC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.3056
p.A418V	TCGA-B5-A0JY	UCEC	TCGA	PPGY	ITCH	410:413	Mutation rewiring degron network	0.1944
p.A418V	DO43041	UCEC	ICGC	PPGY	ITCH	410:413	Mutation rewiring degron network	0.1944
p.A418V	ACH-000973	Bladder Cancer	CCLE	PPGY	ITCH	410:413	Mutation rewiring degron network	0.1944
p.A418V	639-V	urinary tract	COSMIC	PPGY	ITCH	410:413	Mutation rewiring degron network	0.1944
p.R220Q	TCGA-CV-5966	HNSC	TCGA	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation rewiring degron network	0.0833
p.R220Q	DO14950	HNSC	ICGC	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation rewiring degron network	0.0833
p.A214V	TCGA-DD-A3A2	LIHC	TCGA	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation rewiring degron network	0.25
p.A214V	DO44881	LIHC	ICGC	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation rewiring degron network	0.25
p.L191M	TCGA-DK-A2I4	BLCA	TCGA	PLSSS	DEG_SPOP_SBC_1	185:189	Mutation rewiring degron network	0.2778
p.L191M	TCGA-DK-A2I4	BLCA	TCGA	NVYSSDP	CBL_PTK	192:198	Mutation rewiring degron network	0.3056
p.L191M	DO465	BLCA	ICGC	PLSSS	DEG_SPOP_SBC_1	185:189	Mutation rewiring degron network	0.2778
p.L191M	DO465	BLCA	ICGC	NVYSSDP	CBL_PTK	192:198	Mutation rewiring degron network	0.3056
p.E415K	TCGA-E6-A1LX	UCEC	TCGA	PPGY	ITCH	410:413	Mutation rewiring degron network	0.2778
p.E415K	DO41020	UCEC	ICGC	PPGY	ITCH	410:413	Mutation rewiring degron network	0.2778
p.P410L	TCGA-EE-A2GC	SKCM	TCGA	PPGY	ITCH	410:413	Mutation altering degron motif	0.7582
p.P198S	TCGA-EE-A2MJ	SKCM	TCGA	NVYSSDP	CBL_PTK	192:198	Mutation altering degron motif	0.6752
p.P198S	DO220877	MELA	ICGC	NVYSSDP	CBL_PTK	192:198	Mutation altering degron motif	0.6752
p.P198S	DO38099	SKCM	ICGC	NVYSSDP	CBL_PTK	192:198	Mutation altering degron motif	0.6752
p.S211Y	TCGA-FD-A6TC	BLCA	TCGA	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation altering degron motif	0.8231
p.R405K	TCGA-FS-A4F0	SKCM	TCGA	PPGY	ITCH	410:413	Mutation rewiring degron network	0.1944
p.S423F	TCGA-W3-AA1V	SKCM	TCGA	PPGY	ITCH	410:413	Mutation blocking phosphorylation signal	0.5
p.S423F	DO51276	SKCM	ICGC	PPGY	ITCH	410:413	Mutation blocking phosphorylation signal	0.5
p.E408K	TCGA-ZF-AA4W	BLCA	TCGA	PPGY	ITCH	410:413	Mutation rewiring degron network	0.2778
p.S126Y	DO49755	BLCA	ICGC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.2222
p.V130M	DO228483	BRCA	ICGC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation altering degron motif	0.7208
p.S211F	DO52699	CLLE	ICGC	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation altering degron motif	0.9093
p.S211F	DO10809	EOPC	ICGC	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation altering degron motif	0.9093
p.R218H	DO228935	COCA	ICGC	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation rewiring degron network	0.1389
p.S210F	DO224628	COCA	ICGC	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation altering degron motif	0.7982
p.A121D	DO233804	GACA	ICGC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0833
p.N188K	DO229036	LICA	ICGC	PLSSS	DEG_SPOP_SBC_1	185:189	Mutation altering degron motif	0.6918
p.H129N	DO229037	LICA	ICGC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.3056
p.D215E	DO229041	LICA	ICGC	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation rewiring degron network	0.2222
p.H216D	DO23456	LINC	ICGC	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation rewiring degron network	0.1944
p.S133F	DO220859	MELA	ICGC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation altering degron motif	0.9093
p.S423T	DO222702	MELA	ICGC	PPGY	ITCH	410:413	Mutation blocking phosphorylation signal	0.5
p.P178H	DO37442	SKCM	ICGC	PLSSS	DEG_SPOP_SBC_1	185:189	Mutation rewiring degron network	0.1389
p.T208A	DO229213	THCA	ICGC	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation altering degron motif	0.6028
p.P185A	DO229224	THCA	ICGC	PLSSS	DEG_SPOP_SBC_1	185:189	Mutation altering degron motif	0.6392
p.R186H	DO43891	UCEC	ICGC	PLSSS	DEG_SPOP_SBC_1	185:189	Mutation altering degron motif	0.8244
p.R186H	DO42713	UCEC	ICGC	PLSSS	DEG_SPOP_SBC_1	185:189	Mutation altering degron motif	0.8244
p.V144M	SIDM00216	Colorectal Carcinoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM00611	Kidney Carcinoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM01197	Colorectal Carcinoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM00491	Thyroid Gland Carcinoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM01030	Esophageal Squamous Cell Carcinoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM00555	Glioblastoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM00308	Chronic Myelogenous Leukemia	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM00231	Kidney Carcinoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM00569	Osteosarcoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM00193	Colorectal Carcinoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM00002	Neuroblastoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM00301	Pancreatic Carcinoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM00351	Oral Cavity Carcinoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM00024	Non-Cancerous	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM00498	Colorectal Carcinoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM00018	Acute Myeloid Leukemia	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM01031	Esophageal Squamous Cell Carcinoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM00233	T-Lymphoblastic Leukemia	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM00316	Glioblastoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM01570	Ovarian Carcinoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM01412	Oral Cavity Carcinoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM01472	Hepatocellular Carcinoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM00161	Biliary Tract Carcinoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM00163	Biliary Tract Carcinoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM01448	Head and Neck Carcinoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM01454	Kidney Carcinoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.V144M	SIDM01215	Ovarian Carcinoma	GDSC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0556
p.S415N	SIDM00985	Burkitt's Lymphoma	GDSC	PPGY	ITCH	410:413	Mutation rewiring degron network	0.2778
p.S415N	SIDM00674	Non-Cancerous	GDSC	PPGY	ITCH	410:413	Mutation rewiring degron network	0.2778
p.S415N	SIDM00675	Breast Carcinoma	GDSC	PPGY	ITCH	410:413	Mutation rewiring degron network	0.2778
p.V221I	SIDM01144	Gastric Carcinoma	GDSC	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation rewiring degron network	0.0556
p.V221I	NCI-SNU-5	stomach	COSMIC	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation rewiring degron network	0.0556
p.M194I	SIDM00727	Non-Small Cell Lung Carcinoma	GDSC	NVYSSDP	CBL_PTK	192:198	Mutation altering degron motif	0.7618
p.M194I	NCI-H2342	lung	COSMIC	NVYSSDP	CBL_PTK	192:198	Mutation altering degron motif	0.7618
p.G423C	SIDM00100	Mesothelioma	GDSC	PPGY	ITCH	410:413	Mutation blocking phosphorylation signal	0.5
p.G423C	H2595	pleura	COSMIC	PPGY	ITCH	410:413	Mutation blocking phosphorylation signal	0.5
p.G220S	SIDM01228	Melanoma	GDSC	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation rewiring degron network	0.0833
p.G220S	CHL-1	skin	COSMIC	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation rewiring degron network	0.0833
p.P212A	SIDM01691	Chronic Myelogenous Leukemia	GDSC	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation rewiring degron network	0.3056
p.P198A	ACH-000321	Leukemia	CCLE	NVYSSDP	CBL_PTK	192:198	Mutation altering degron motif	0.7503
p.S209N	ACH-000922	Leukemia	CCLE	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation altering degron motif	0.7069
p.G206S	ACH-000931	Skin Cancer	CCLE	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation rewiring degron network	0.3056
p.G206S	ACH-000931	Skin Cancer	CCLE	NVYSSDP	CBL_PTK	192:198	Mutation rewiring degron network	0.1111
p.G206S	ACH-001024	Skin Cancer	CCLE	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation rewiring degron network	0.3056
p.G206S	ACH-001024	Skin Cancer	CCLE	NVYSSDP	CBL_PTK	192:198	Mutation rewiring degron network	0.1111
p.G206S	CHL-1	skin	COSMIC	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation rewiring degron network	0.3056
p.G206S	CHL-1	skin	COSMIC	NVYSSDP	CBL_PTK	192:198	Mutation rewiring degron network	0.1111
p.M180I	ACH-000951	Lung Cancer	CCLE	PLSSS	DEG_SPOP_SBC_1	185:189	Mutation rewiring degron network	0.1944
p.M180I	NCI-H2342	lung	COSMIC	PLSSS	DEG_SPOP_SBC_1	185:189	Mutation rewiring degron network	0.1944
p.A139V	ACH-000998	Colon/Colorectal Cancer	CCLE	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.1944
p.A139V	CW-2	large intestine	COSMIC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.1944
p.D407V	ACH-001957	Bone Cancer	CCLE	PPGY	ITCH	410:413	Mutation rewiring degron network	0.25
p.G409C	ACH-002127	Lung Cancer	CCLE	PPGY	ITCH	410:413	Mutation rewiring degron network	0.3056
p.G409C	H2595	pleura	COSMIC	PPGY	ITCH	410:413	Mutation rewiring degron network	0.3056
p.P411A	ACH-002370	Non-Cancerous	CCLE	PPGY	ITCH	410:413	Mutation altering degron motif	0.7503
p.P410T	KU-19-19	urinary tract	COSMIC	PPGY	ITCH	410:413	Mutation altering degron motif	0.7031
p.P410T	HuO-3N1	bone	COSMIC	PPGY	ITCH	410:413	Mutation altering degron motif	0.7031
p.G121S	CHL-1	skin	COSMIC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation rewiring degron network	0.0833
p.V207I	NCI-SNU-5	stomach	COSMIC	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation altering degron motif	0.7076
p.M203I	Hs766T	pancreas	COSMIC	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation rewiring degron network	0.2222
p.M203I	Hs766T	pancreas	COSMIC	NVYSSDP	CBL_PTK	192:198	Mutation rewiring degron network	0.1944
p.H216R	IST-SL1	lung	COSMIC	VTSSS	DEG_SPOP_SBC_1	207:211	Mutation rewiring degron network	0.1944
p.V122I	NCI-SNU-5	stomach	COSMIC	VLSSS	DEG_SPOP_SBC_1	130:134	Mutation blocking phosphorylation signal	0.5556

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

TFEB

UniProt ID: P19484

Entrez ID: 7942

Protein name: Transcription factor EB (Class E basic helix-loop-helix protein 35) (bHLHe35)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for TFEB in