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| | Functional domains in the TFEB protein. |
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| 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. |
| Entity | 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/Mutated Gene | Alpha/TFEB, both fusion genes are expressed; 5'-Alpha-TFEB-3' fusion transcript contains the entire open reading frame of TFEB. |
| Abnormal 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. |
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| A helix-loop-helix protein related to the immunoglobulin E box-binding proteins. |
| Carr CS, Sharp PA |
| Molecular and cellular biology. 1990 ; 10 (8) : 4384-4388. |
| PMID 2115126 |
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| TFEB has DNA-binding and oligomerization properties of a unique helix-loop-helix/leucine-zipper family. |
| Fisher DE, Carr CS, Parent LA, Sharp PA |
| Genes & development. 1991 ; 5 (12A) : 2342-2352. |
| PMID 1748288 |
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| microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family. |
| Hemesath TJ, Steingrˆ‚msson E, McGill G, Hansen MJ, Vaught J, Hodgkinson CA, Arnheiter H, Copeland NG, Jenkins NA, Fisher DE |
| Genes & development. 1994 ; 8 (22) : 2770-2780. |
| PMID 7958932 |
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| The bHLH-Zip transcription factor Tfeb is essential for placental vascularization. |
| Steingrˆ‚msson E, Tessarollo L, Reid SW, Jenkins NA, Copeland NG |
| Development (Cambridge, England). 1998 ; 125 (23) : 4607-4616. |
| PMID 9806910 |
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| A 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, Hawkins A, Griffin CA, Goldstein JD, Haas M, Beckwith JB, Mankinen CB, Perlman EJ |
| The American journal of pathology. 2001 ; 158 (6) : 2089-2096. |
| PMID 11395386 |
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| Recent advances in pediatric renal neoplasia. |
| Argani P, Ladanyi M |
| Advances in anatomic pathology. 2003 ; 10 (5) : 243-260. |
| PMID 12973047 |
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| Distinctive neoplasms characterised by specific chromosomal translocations comprise a significant proportion of paediatric renal cell carcinomas. |
| Argani P, Ladanyi M |
| Pathology. 2003 ; 35 (6) : 492-498. |
| PMID 14660099 |
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| Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation. |
| Davis IJ, Hsi BL, Arroyo JD, Vargas SO, Yeh YA, Motyckova G, Valencia P, Perez-Atayde AR, Argani P, Ladanyi M, Fletcher JA, Fisher DE |
| Proceedings of the National Academy of Sciences of the United States of America. 2003 ; 100 (10) : 6051-6056. |
| PMID 12719541 |
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| Upregulation of the transcription factor TFEB in t(6;11)(p21;q13)-positive renal cell carcinomas due to promoter substitution. |
| Kuiper RP, Schepens M, Thijssen J, van Asseldonk M, van den Berg E, Bridge J, Schuuring E, Schoenmakers EF, van Kessel AG |
| Human molecular genetics. 2003 ; 12 (14) : 1661-1669. |
| PMID 12837690 |
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