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IID00789
UniprotP19532
ProteinTranscription factor E3
GeneTFE3
OrganismHomo sapiens
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
575
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 360-430 Homo tetramer :
 Evidence X-RAY 7f09 D Reference
       Region 7f09 D 360-374 order
       Region 7f09 D 375-382 disorder
       Region 7f09 D 383-430 order
 Evidence X-RAY 7f09 C Reference
       Region 7f09 C 360-375 order
       Region 7f09 C 376-381 disorder
       Region 7f09 C 382-430 order
 Evidence X-RAY 7f09 B Reference
       Region 7f09 B 360-374 order
       Region 7f09 B 375-380 disorder
       Region 7f09 B 381-430 order
 Evidence X-RAY 7f09 A Reference
       Region 7f09 A 360-430 order
Seqphosphorylation
    47-47 Phosphoserine; by MTOR
    542-542 Phosphoserine
    321-321 Phosphoserine; by MTOR
    548-548 Phosphoserine
    554-554 Phosphoserine
    556-556 Phosphoserine
    560-560 Phosphoserine
    568-568 Phosphoserine
 
Prediction
NeProc
Disorder 1-112,141-275,281-342,434-575
Order 113-140,276-280,343-433
ProS 21-28,35-72,174-185,242-251,256-275,281-308,326-329,434-436,500-521,539-575
AlphaFold
Disorder 1-110,138-185,206-258,273-333,443-575
Order 111-137,186-205,259-272,334-442
Pfam Hmmer
PF00010 347-400 2.7e-18
SEG 67-105 ,107-112 ,115-161 ,218-231 ,255-274 ,447-459 ,480-503 ,527-542 ,546-570
Function
Function in SwissProt
Transcription factor that acts as a master regulator of lysosomal biogenesis and immune response (PubMed:2338243, PubMed:24448649, PubMed:29146937, PubMed:30733432, PubMed:31672913, PubMed:37079666). 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 (PubMed:24448649). 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 inactivation (PubMed:24448649, PubMed:31672913, PubMed:36608670). Upon starvation or lysosomal stress, inhibition of MTOR induces TFE3 dephosphorylation, resulting in transcription factor activity (PubMed:24448649, PubMed:31672913, PubMed:36608670). 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:24448649). Maintains the pluripotent state of embryonic stem cells by promoting the expression of genes such as ESRRB; mTOR-dependent TFE3 cytosolic retention and inactivation 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). TFE3 activity is also involved in the inhibition of neuronal progenitor differentiation (By similarity). 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). 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). Promotes TGF-beta-induced transcription of COL1A2; via its interaction with TSC22D1 at E-boxes in the gene proximal promoter (By similarity). May regulate lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1 (PubMed:29146937).