TFEB (transcription factor EB)

2004-05-01   Roland P Kuiper 

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

Identity

HGNC
LOCATION
6p21.1
LOCUSID
ALIAS
ALPHATFEB,BHLHE35,TCFEB
FUSION GENES

DNA/RNA

Atlas Image
Genomic organization of TFEB gene.

Description

TFEB gene contains 8 coding exons and 7 alternative first exons that are differentially expressed.

Transcription

Alternative first exon usage points towards the existence of up to seven alternative promoters. Alternative splicing of exon 3 (encoding an acidic activation domain) similar to the closely related TFE3, TFEC, and MiTF genes.

Proteins

Atlas Image
Functional domains in the TFEB protein.

Description

490 amino acids; 65 kDa; N-terminal Gln-rich stretch (Gln, exon 2), N-term acidic transcriptional activation domain (AAD, exon 3), basic helix-loop-helix region (bHLH, exon 6-8), leucine zipper (LZ, exon 8), proline-rich activation domain ( ProAD, exon 9), Ser-rich stretch (Ser)

Expression

Wide in fetal and adult tissues, although the various TFEB transcript variants are expressed in a tissue-restricted manner: TFEB-A is enriched in placenta, TFEB-F in spleen, and TFEB-E and TFEB-G in brain.

Localisation

Nucleus

Function

Transcription factor; member of the basic-helix-loop-helix leucine-zipper transcription factor MiTF/TFE family (also known as the MiT family), which also contains MiTF, TFEC, and TFE3. The four members form homo- and/or heterodimers to bind the Ebox core sequence CAYGTG; the helix-loop-helix - leucine zipper region is implicated in DNA binding and dimerization (homo and heterodimerizations); mice which lack TFEB die due to defects in placental vascularization.

Homology

High homology to the other MiTF/TFE members TFE3, TFEC and MiTF, homologous to myc family of bHLH transcription factors.

Implicated in

Entity name
Renal cell carcinoma with t(6;11)(p21;q13) -> Alpha/TFEB gene fusion
Disease
Clear cell renal cell carcinomas
Prognosis
Limited follow-up available, prognosis appears to be good; no reports of developed metastases
Cytogenetics
t(6;11)(p21;q13), usually as the sole cytogenetic anomaly.
Hybrid gene
Alpha/TFEB, both fusion genes are expressed; 5-Alpha-TFEB-3 fusion transcript contains the entire open reading frame of TFEB.
Fusion protein
No fusion protein, the Alpha gene is a non-protein-encoding transcript.
Oncogenesis
Highly induced expression of full-length TFEB protein due to promoter substitution in the Alpha-TFEB fusion gene.

Bibliography

Pubmed IDLast YearTitleAuthors
113953862001A distinctive pediatric renal neoplasm characterized by epithelioid morphology, basement membrane production, focal HMB45 immunoreactivity, and t(6;11)(p21.1;q12) chromosome translocation.Argani P et al
146600992003Distinctive neoplasms characterised by specific chromosomal translocations comprise a significant proportion of paediatric renal cell carcinomas.Argani P et al
21151261990A helix-loop-helix protein related to the immunoglobulin E box-binding proteins.Carr CS et al
127195412003Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation.Davis IJ et al
17482881991TFEB has DNA-binding and oligomerization properties of a unique helix-loop-helix/leucine-zipper family.Fisher DE et al
79589321994microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family.Hemesath TJ et al
128376902003Upregulation of the transcription factor TFEB in t(6;11)(p21;q13)-positive renal cell carcinomas due to promoter substitution.Kuiper RP et al
98069101998The bHLH-Zip transcription factor Tfeb is essential for placental vascularization.Steingrímsson E et al

Other Information

Locus ID:

NCBI: 7942
MIM: 600744
HGNC: 11753
Ensembl: ENSG00000112561

Variants:

dbSNP: 7942
ClinVar: 7942
TCGA: ENSG00000112561
COSMIC: TFEB

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000112561ENST00000230323P19484
ENSG00000112561ENST00000230323A0A024RCY3
ENSG00000112561ENST00000343317B0QYS7
ENSG00000112561ENST00000358871B0QYS6
ENSG00000112561ENST00000373033P19484
ENSG00000112561ENST00000373033A0A024RCY3
ENSG00000112561ENST00000394283B1AKB4
ENSG00000112561ENST00000403298P19484
ENSG00000112561ENST00000403298A0A024RCY3
ENSG00000112561ENST00000406563B1AKB5
ENSG00000112561ENST00000416140B1AKB2
ENSG00000112561ENST00000419396A0A1B0GXL9
ENSG00000112561ENST00000419574B1AKB1
ENSG00000112561ENST00000420312P19484
ENSG00000112561ENST00000424495Q709A9
ENSG00000112561ENST00000425401Q709A8
ENSG00000112561ENST00000433032B1AKA7
ENSG00000112561ENST00000445214B1AKA9
ENSG00000112561ENST00000445700B1AKA7

Expression (GTEx)

0
10
20
30
40
50
60

Pathways

PathwaySourceExternal ID
Mitophagy - animalKEGGko04137
Mitophagy - animalKEGGhsa04137

References

Pubmed IDYearTitleCitations
216170402011TFEB links autophagy to lysosomal biogenesis.856
195564632009A gene network regulating lysosomal biogenesis and function.699
223439432012A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB.562
226924232012The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis.385
225760152012MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB.326
257209632015Lysosomal calcium signalling regulates autophagy through calcineurin and ​TFEB.297
217528292011Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways.263
218894212011Transcriptional activation of lysosomal exocytosis promotes cellular clearance.213
227866822012PGC-1α rescues Huntington's disease proteotoxicity by preventing oxidative stress and promoting TFEB function.153
272523822016TFEB at a glance.124

Citation

Roland P Kuiper

TFEB (transcription factor EB)

Atlas Genet Cytogenet Oncol Haematol. 2004-05-01

Online version: http://atlasgeneticsoncology.org/gene/531/tfeb