TFE3 (transcription factor E3)

2004-05-01   Roland P Kuiper 

Identity

HGNC
LOCATION
Xp11.23
LOCUSID
FUSION GENES

DNA/RNA

Atlas Image

Description

8 exons

Transcription

differential splicing removing exon 3 (with dominant negative activity of the resulting protein)

Proteins

Atlas Image

Description

743 amino acids; 80 kDa; N-term acidic transcriptional activation domain (domain 260-271, exon 3), helix-loop-helix (344 -400), leucine zipper (409-430), and a proline/arginine rich sequence (575-743) C-term

Expression

wide; in fetal and adult tissues

Localisation

nucleus

Function

transcription factor; member of the basic helix-loop-helix family (b-HLH) of transcription factors primarily found to bind to the immunoglobulin enchancer muE3 motif, Ig K enhancers and Ig H variable regions promotors; the helix-loop-helix - leucine zipper region is implicated in DNA binding and dimerization (homo and heterodimerizations); mice which lack TFE3 in their B and T lymphocytes reconstitute the B- and T-cell compartments, but IgM levels are reduced

Homology

to other members of the myc family of helix-loop-helix transcription factors

Implicated in

Entity name
t(X;1)(p11.2;q21.2) in renal cell carcinoma --> PRCC/TTFE3
Prognosis
overall 5-yr survival rate around 85%
Hybrid gene
5 PRCC- 3 TFE3; variable breakpoint in PRCC; breakpoint in the 1st intron of TFE3
Fusion protein
N-term PRCC with the proline rich sequence fused to most of TFE3, including the acidic transcriptional activation domain, the helix-loop-helix, and the leucine zipper; the reciprocal TFE3-PRCC is expressed; it is to be noted that the normal TFE3 transcript is lost in female patients
Atlas Image
Oncogenesis
PRCCTFE3 appears to be the fusion product that is most critical for the development of papillary renal cell carcinomas; it is a three-fold better transactivator than wild-type TFE3 and shows the characteristics associated with malignant trannsformation
Entity name
t(X;1)(p11.2;p34) in renal cell carcinoma --> PSF/TFE3
Disease
t(X;1)(p11.2;p34) has only been found in a handfull cases of papillary renal cell carcinoma
Hybrid gene
5 PSF- 3 TFE3
Atlas Image
Fusion protein
N-term PSF and most of it fused to the DNA binding domains of TFE3 (excluding the acidic transcriptional activation domain, including the C-term helix-loop-helix, and the leucine zipper); no TFE3-PSF reciprocal transcript, as the der(X) t(X;1) is missing; the normal TFE3 transcript is found
Entity name
inv(X)(p11.2q12) in renal cell carcinoma --> NONO/TFE3
Disease
only one case of papillary renal cell carcinoma
Hybrid gene
5 NONO- 3 TFE3
Atlas Image
Fusion protein
N-term NONO and most of it except the C-term proline rich sequence fused to the DNA binding domains of TFE3 (excluding the acidic transcriptional activation domain, including the C-term helix-loop-helix, and the leucine zipper); the reciprocal transcript is found
Entity name
Cytogenetics
der(X)t(X;17)(p11;q25) is consistently involved; it implicates: 1- the formation of a hybrid gene at the breakpoint, and also, 2- gain in Xp11-pter sequences, and loss of heterozygocity in 11q25-qter, with possible implications
Hybrid gene
5 ASPSCR1-3 TFE3; the reciprocal 5 TFE3 - 3 ASPSCR1 is most often absent. ASPSCR1 is fused in frame to TFE3 exon 3 or 4
Fusion protein
NH2 term ASPSCR1, fused to the C term of TFE3
Oncogenesis
might combine the effect of a fusion protein to that of gene(s) dosage
Disease
a subset of renal cell carcinoma, which presents with a combination of alveolar soft part sarcoma-like features and epithelial features is found to carry this anomaly
Cytogenetics
balanced t(X;17)(p11.2;q25), in contrast with what is found in the alveolar soft part sarcoma (see above)
Hybrid gene
5 ASPSCR1-3 TFE3
Fusion protein
NH2 term ASPSCR1, fused to the C term of TFE3
Entity name
other Xp11 involvements in renal cell carcinoma (t(X;10)(p11;q23), etc ...) are likely to implicate TFE3

Breakpoints

Atlas Image

Bibliography

Pubmed IDLast YearTitleAuthors
114384652001Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents.Argani P et al
20449531991The leucine zipper of TFE3 dictates helix-loop-helix dimerization specificity.Beckmann H et al
93939821997Fusion of splicing factor genes PSF and NonO (p54nrb) to the TFE3 gene in papillary renal cell carcinoma.Clark J et al
113588362001Fusion of a novel gene, RCC17, to the TFE3 gene in t(X;17)(p11.2;q25.3)-bearing papillary renal cell carcinomas.Heimann P et al
112445032001The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25.Ladanyi M et al
91548321997The absence of the transcription activator TFE3 impairs activation of B cells in vivo.Merrell K et al
18407051991A dominant negative form of transcription activator mTFE3 created by differential splicing.Roman C et al
88724741996The t(X;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a novel gene PRCC to the TFE3 transcription factor gene.Sidhar SK et al
113138852001Transformation capacities of the papillary renal cell carcinoma-associated PRCCTFE3 and TFE3PRCC fusion genes.Weterman MA et al
106449812000Nuclear localization and transactivating capacities of the papillary renal cell carcinoma-associated TFE3 and PRCC (fusion) proteins.Weterman MJ et al

Other Information

Locus ID:

NCBI: 7030
MIM: 314310
HGNC: 11752
Ensembl: ENSG00000068323

Variants:

dbSNP: 7030
ClinVar: 7030
TCGA: ENSG00000068323
COSMIC: TFE3

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000068323ENST00000315869P19532
ENSG00000068323ENST00000315869A0A024QZ23
ENSG00000068323ENST00000493583P19532

Expression (GTEx)

0
50
100
150

Pathways

PathwaySourceExternal ID
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202
Mitophagy - animalKEGGko04137
Mitophagy - animalKEGGhsa04137

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
244486492014The nutrient-responsive transcription factor TFE3 promotes autophagy, lysosomal biogenesis, and clearance of cellular debris.161
237372132013Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma.70
281650112017mTORC1-independent TFEB activation via Akt inhibition promotes cellular clearance in neurodegenerative storage diseases.68
208712142010A distinctive subset of PEComas harbors TFE3 gene fusions.61
268137912016TFEB and TFE3 are novel components of the integrated stress response.61
215555182011The BTB and CNC homology 1 (BACH1) target genes are involved in the oxidative stress response and in control of the cell cycle.60
271710642016TFEB and TFE3 cooperate in the regulation of the innate immune response in activated macrophages.57
250488602014Molecular genetics and cellular features of TFE3 and TFEB fusion kidney cancers.49
167662662006Oncogenic MITF dysregulation in clear cell sarcoma: defining the MiT family of human cancers.46
127482762003Identification of E-box factor TFE3 as a functional partner for the E2F3 transcription factor.45

Citation

Roland P Kuiper

TFE3 (transcription factor E3)

Atlas Genet Cytogenet Oncol Haematol. 2004-05-01

Online version: http://atlasgeneticsoncology.org/gene/86/tfe3

Historical Card

2001-08-01 TFE3 (transcription factor E3) by  Jean-Loup Huret 

Dept of Human Genetics-417, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands

1999-01-01 TFE3 (transcription factor E3) by  Jean-Loup Huret,François Desangles 

Dept of Human Genetics-417, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands