Atlas of Genetics and Cytogenetics in Oncology and Haematology
USP6 (ubiquitin specific protease 6 (Tre-2 oncogene))
| Identity |
| Other names | TRE2 |
| TRE17 | |
| Hugo | USP6 |
| Location | 17p13 |
| Note | The gene is the result of a recent evolutionary fusion of two other genes - TBC1D3 (PRC17) on chromosome 17q12 and USP32 (NY-REN-60) on chromosome 17q22 (see below). |
| DNA/RNA |
| Description | 30 exons spanning 47 kb of genomic DNA. Exons 1 to 14 are derived from the TBC1D3 (PRC17), and exons 15 to 30 are derived from the USP32 (NY-REN-60). |
| Transcription | The gene is transcribed from telomere to centromere. The coding region starts on exon 2 but many splicing variants have been identified in the untranslated exon 1. There are at least two major transcripts with an approximate lenght of 8 kb. |
| Protein |
 | |
| Description | USP6 encodes for a 1406 aminoacid protein containing two major domains: TBC (from TRE2-Bub2-Cdc16), which encodes a GTPase-activating protein of the Rab family of GTPases, and a UBP domain with a ubiquitin specific protease activity. A USP6 splicing variant, also known as onco-TRE17 or TRE17-oncoš, encodes a 786 aminoacid protein with a truncated UBP domain. See figure 1. |
| Expression | Among normal tissues, USP6 seems to primarily expressed in testes. |
| Localisation | Cytoplasmic protein. |
| Function | USP6 function is still poorly understood but recent evidence has shown that USP6 is involved in endocytic trafficking. USP6 seems to operate in the same pathway controlled by Arf6 GTPase, which has been linked to mitogenic signaling and invasive behavior. |
| Homology | While the N-terminal portion of USP6 is highly homologous to PRC17 (89% identity), the C-terminal end is highly homologous to USP32 (97% identity). |
| Implicated in |
| Disease | Aneurysmal Bone Cyst or Aneurysmal Bone Tumor |
| Cytogenetics | Rearrangements of 17p13 with different partner chromosomes. |
 | |
| Hybrid/Mutated Gene | USP6 fusion genes are formed by juxtaposition of USP6 coding sequences to the promoter regions of several partner genes, which lead to USP6 transcriptional upregulation. There is no fusion protein. |
| Breakpoints |
 | |
| External links |
| Bibliography |
| A rearranged transforming gene, tre, is made up of human sequences derived from chromosome regions 5q, 17q and 18q. |
| Huebner K, Cannizzaro LA, Nakamura T, Hillova J, Mariage-Samson R, Hecht F, Hill M, Croce CM |
| Oncogene. 1988 ; 3 (4) : 449-455. |
| PMID 3274085 |
| Molecular cloning of a novel oncogene generated by DNA recombination during transfection. |
| Nakamura T, Hillova J, Mariage-Samson R, Hill M |
| Oncogene research. 1988 ; 2 (4) : 357-370. |
| PMID 2840623 |
| A novel transcriptional unit of the tre oncogene widely expressed in human cancer cells. |
| Nakamura T, Hillova J, Mariage-Samson R, Onno M, Huebner K, Cannizzaro LA, Boghosian-Sell L, Croce CM, Hill M |
| Oncogene. 1992 ; 7 (4) : 733-741. |
| PMID 1565468 |
| Endocytosis of epidermal growth factor receptor regulated by Grb2-mediated recruitment of the Rab5 GTPase-activating protein RN-tre. |
| Martinu L, Santiago-Walker A, Qi H, Chou MM |
| The Journal of biological chemistry. 2002 ; 277 (52) : 50996-51002. |
| PMID 12399475 |
| The TRE17 oncogene encodes a component of a novel effector pathway for Rho GTPases Cdc42 and Rac1 and stimulates actin remodeling. |
| Masuda-Robens JM, Kutney SN, Qi H, Chou MM |
| Molecular and cellular biology. 2003 ; 23 (6) : 2151-2161. |
| PMID 12612085 |
| The Tre2 (USP6) oncogene is a hominoid-specific gene. |
| Paulding CA, Ruvolo M, Haber DA |
| Proceedings of the National Academy of Sciences of the United States of America. 2003 ; 100 (5) : 2507-2511. |
| PMID 12604796 |
| The TBC (Tre-2/Bub2/Cdc16) domain protein TRE17 regulates plasma membrane-endosomal trafficking through activation of Arf6. |
| Martinu L, Masuda-Robens JM, Robertson SE, Santy LC, Casanova JE, Chou MM |
| Molecular and cellular biology. 2004 ; 24 (22) : 9752-9762. |
| PMID 15509780 |
| USP6 (Tre2) fusion oncogenes in aneurysmal bone cyst. |
| Oliveira AM, Hsi BL, Weremowicz S, Rosenberg AE, Dal Cin P, Joseph N, Bridge JA, Perez-Atayde AR, Fletcher JA |
| Cancer research. 2004 ; 64 (6) : 1920-1923. |
| PMID 15026324 |
| USP6 and CDH11 oncogenes identify the neoplastic cell in primary aneurysmal bone cysts and are absent in so-called secondary aneurysmal bone cysts. |
| Oliveira AM, Perez-Atayde AR, Inwards CY, Medeiros F, Derr V, Hsi BL, Gebhardt MC, Rosenberg AE, Fletcher JA |
| The American journal of pathology. 2004 ; 165 (5) : 1773-1780. |
| PMID 15509545 |
| Aneurysmal bone cyst variant translocations upregulate USP6 transcription by promoter swapping with the ZNF9, COL1A1, TRAP150, and OMD genes. |
| Oliveira AM, Perez-Atayde AR, Dal Cin P, Gebhardt MC, Chen CJ, Neff JR, Demetri GD, Rosenberg AE, Bridge JA, Fletcher JA |
| Oncogene. 2005 ; 24 (21) : 3419-3426. |
| PMID 15735689 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 04-2005 | Andre M Oliveira, Margaret Chou |
| Department of Pathology and Laboratory Medicine, Mayo Clinic and Mayo Foundation, 200 First Street SW, Rochester, MN 55905, USA |
| Citation |
| This paper should be referenced as such : |
| Oliveira AM, Chou M . USP6 (ubiquitin specific protease 6 (Tre-2 oncogene)). Atlas Genet Cytogenet Oncol Haematol. April 2005 . URL : http://AtlasGeneticsOncology.org/Genes/USP6ID530ch17p13.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed Jul 2 08:27:55 2008 |
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