DegronMD - P19532(TFE3)

FUNCTION: Transcription factor that acts as a master regulator of lysosomal biogenesis and immune response (PubMed:2338243, PubMed:29146937, PubMed:30733432, 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 TFEB or MITF (By similarity). Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, TFE3 phosphorylation by MTOR promotes its cytosolic retention and subsequent inactivation (PubMed:31672913). Upon starvation or lysosomal stress, inhibition of MTOR induces TFE3 dephosphorylation, resulting in nuclear localization and transcription factor activity (PubMed:31672913). In association with TFEB, 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 MUE3 box, a subset of E-boxes, present in the immunoglobulin enhancer (PubMed:2338243). It also binds very well to a USF/MLTF site (PubMed:2338243). May regulate lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1 (PubMed:29146937). Acts as a positive regulator of browning of adipose tissue by promoting expression of target genes; mTOR-dependent phosphorylation promotes cytoplasmic retention of TFE3 and inhibits browning of adipose tissue (By similarity). Maintains the pluripotent state of embryonic stem cells by promoting the expression of genes such as ESRRB; mTOR-dependent nuclear exclusion promotes exit from pluripotency (By similarity). Required to maintain the naive pluripotent state of hematopoietic stem cell; mTOR-dependent cytoplasmic retention of TFE3 promotes the exit of hematopoietic stem cell from pluripotency (PubMed:30733432). {ECO:0000250|UniProtKB:Q64092, ECO:0000269|PubMed:2338243, ECO:0000269|PubMed:29146937, ECO:0000269|PubMed:30733432, ECO:0000269|PubMed:31672913}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.S321F	TCGA-17-Z026	LUAD	TCGA	VATPAIT	DEG_SCF_FBW7_1	311:317	Mutation blocking phosphorylation signal	0.6667
p.G100C	TCGA-58-8388	LUSC	TCGA	AMSSS	DEG_SPOP_SBC_1	105:109	Mutation rewiring degron network	0.1944
p.V311M	TCGA-AJ-A3BH	UCEC	TCGA	VATPAIT	DEG_SCF_FBW7_1	311:317	Mutation altering degron motif	0.6097
p.V311M	DO41638	UCEC	ICGC	VATPAIT	DEG_SCF_FBW7_1	311:317	Mutation altering degron motif	0.6097
p.S111L	TCGA-EB-A431	SKCM	TCGA	AMSSS	DEG_SPOP_SBC_1	105:109	Mutation rewiring degron network	0.2778
p.S111L	DO37671	SKCM	ICGC	AMSSS	DEG_SPOP_SBC_1	105:109	Mutation rewiring degron network	0.2778
p.M106R	TCGA-EE-A2MS	SKCM	TCGA	AMSSS	DEG_SPOP_SBC_1	105:109	Mutation altering degron motif	0.7521
p.M106R	DO37567	SKCM	ICGC	AMSSS	DEG_SPOP_SBC_1	105:109	Mutation altering degron motif	0.7521
p.S107L	TCGA-FI-A2D5	UCEC	TCGA	AMSSS	DEG_SPOP_SBC_1	105:109	Mutation altering degron motif	0.7667
p.S107L	DO41331	UCEC	ICGC	AMSSS	DEG_SPOP_SBC_1	105:109	Mutation altering degron motif	0.7667
p.L302V	DO1076	BRCA	ICGC	VATPAIT	DEG_SCF_FBW7_1	311:317	Mutation rewiring degron network	0.0833
p.L302M	DO229028	LICA	ICGC	VATPAIT	DEG_SCF_FBW7_1	311:317	Mutation rewiring degron network	0.0833
p.G310D	DO232224	PBCA	ICGC	VATPAIT	DEG_SCF_FBW7_1	311:317	Mutation rewiring degron network	0.3056
p.V114D	DO231495	THCA	ICGC	AMSSS	DEG_SPOP_SBC_1	105:109	Mutation rewiring degron network	0.1944
p.S308N	SIDM00720	Mesothelioma	GDSC	VATPAIT	DEG_SCF_FBW7_1	311:317	Mutation rewiring degron network	0.25

Kaplan plot for TFE3 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

TFE3

UniProt ID: P19532

Entrez ID: 7030

Protein name: Transcription factor E3 (Class E basic helix-loop-helix protein 33) (bHLHe33)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for TFE3 in